The Federal Reserve kept rates unchanged and continues to expect "only gradual increases" in the Fed funds rate.
The U.S. dollar index struggled for direction in volatile trade after the Fed statement release. The euro was last near $1.13 and the yen at 111.4 yen against the greenback.
"The Fed was a non-event. The market continues to decouple on oil prices and the market is continuing to focus on fundamentals and earnings," said Kevin Mahn, president and CIO at Hennion & Walsh Asset Management.
He said the Fed maintained a "hovish" stance, meaning "they're caught in this hybrid hawkish, dovish stance."
Treasury yields held lower after briefly edging off session lows after the Fed statement release.
"Nothing takes June off the table here," said Art Hogan, chief market strategist at Wunderlich Securities. "At the end of the day we want June on the table. We want economic data to be improving."
The Federal Open Market Committee's post-meeting statement said, "economic activity appears to have slowed" and that "growth in household spending has moderated, although households' real income has risen at a solid rate and consumer sentiment remains high."
"I think it's going to be difficult for the Fed to hold court with their prior guidance of two hikes this year," said Brian Muench, vice president of investment management at Allianz Investment Management (AIM).
The latest statement removed the line pointing to risks from global economic and financial developments.
The Dow Jones industrial average extended earlier gains to trade about 50 points higher. Apple contributed the most to declines, with Boeing and Goldman Sachs the top contributor to gains.
The S&P 500 attempted to trade in positive territory again, with telecoms and energy leading, and tech lagging.
U.S. crude oil futures settled up $1.29, or 2.93 percent, at $45.33 a barrel. Earlier, WTI hit a fresh high going back to Nov. 6. WTI initially pared gains after weekly oil inventories from the EIA showed a build of about 2 million barrels.
"Probably the biggest news overhanging the market today (is) Apple's revenue miss and certainly revenue decline, ending a pretty long stretch of growth and it sort of just underscores the trouble the Nasdaq's had over the last few months," said Jack Ablin, chief investment officer at BMO Private Bank.
The Nasdaq is more than 7 percent below its 52-week intraday high, while the Dow and S&P 500 are about 2 percent below that level. On Tuesday, the Nasdaq composite posted its first four-day losing streak since January and information technology joined health care and financials as the only S&P 500 sectors in negative territory for the year so far.
Shares briefly fell more than 8 percent before holding about 6 percent lower in late-morning trade. Trade volume was nearly double average only about 2 hours into the trading session.
The Bank of Japan is set to release its statement on monetary policy Thursday.
Read MoreThe Fed's dance to avoid volatility
In other earnings news, Boeing reported earnings that missed but revenues that beat.
Comcast briefly rose more than 2 percent in morning trade for the most positive impact on the Nasdaq 100. The NBCUniversal and CNBC parent posted earnings that beat on both the top and bottom line. Comcast saw growth across virtually all its business segments, and its biggest first quarter jump in TV customers in nine years.
Separately, overnight there were reports that Comcast is in talks to buy DreamWorks.
In economic news, pending home sales rose 1.4 percent in March.
Total mortgage application volume decreased 4.1 percent last week on a seasonally adjusted basis from the previous week, according to the Mortgage Bankers Association.
The U.S. advance March goods trade deficit came in at $56.90 billion, narrowing from the $62.86 gap reported in the prior month.
Treasury yields held lower after hitting fresh highs since late March Tuesday, with the 2-year yield near 0.84 percent and the 10-year yield around 1.89 percent as of 12:57 p.m. ET.
The U.S. dollar index traded mildly lower, with the euro near $1.133 and the yen at 111.30 yen against the greenback.
Asian stocks closed slightly lower, with the Nikkei 225 and Shanghai composite both ending almost 0.4 percent lower.
Read MoreEarly movers: CMCSA, BHI, UTX, BA, ANTM, NOC, GD, GRMN, AAPL & more
In midday trade, the Dow Jones industrial average gained 21 points, or 0.1 percent, to 18,012, with Boeing leading advancers and Apple the greatest laggard.
The S&P 500 fell 2 points, or 0.1 percent, to 2,081, with information technology leading four sectors lower and utilities the top advancer.
The Nasdaq composite declined 42 points, or 0.86 percent, to 4,846.
The CBOE Volatility Index (VIX), widely considered the best gauge of fear in the market, climbed above 14.5.
About nine stocks advanced for every five advancers on the New York Stock Exchange, with an exchange volume of 435 million and a composite volume of nearly 1.9 billion in midday trade.
U.S. crude oil futures for June delivery were up 1.7 percent near $44.80 a barrel on the New York Mercantile Exchange.
Gold futures for June delivery gained $6.80 to $1,250.20 an ounce as of 1:02 p.m. ET.
—CNBC's Robert Hum contributed to this report.
Earnings: Facebook, Paypal, Ameriprise, Marriott, SanDisk (being bought by WDC), Texas Instruments, Cheesecake Factory
2 p.m. FOMC statement
Earnings: AbbVie, Altria, Bristol-Myers Squibb, Celgene, Colgate-Palmolive, ConocoPhillips, Deutsche Bank, Dow Chemical, Ford, Honda Motor, MasterCard, UPS, Volkswagen, Aetna, CME Group, Domino's Pizza, Marathon Petroleum, Sirius XM Radio, Sony, Time Warner Cable, Viacom, Waste Management, Beazer Homes, Cliffs Natural Resources, Dunkin Brands, Amazon.com, Amgen, Baidu, Gilead Sciences, Samsung Electronics, Eastman Chemical, Expedia, Hartford Fincl., Juniper Networks, LinkedIn, Western Digital, Groupon, LPL Financial, Outerwall, Pandora Media
8:30 a.m. Jobless claims
8:30 .m. Real GDP Q1
10 a.m. Housing vacancies
1 p.m. $28 billion seven-year note auction
Earnings: AstraZeneca, Chevron, Exxon Mobil, Novo Nordisk, Sanofi
6:30 a.m. Dallas Fed President Rob Kaplan
8:30 a.m. Personal income; employment cost index
9:45 a.m. Chicago PMI
10 a.m. Consumer sentiment
*Planner subject to change.