Major averages posted robust gains of more than 1.5 percent across the board in April, with the S&P 500 setting a record intraday high.
Also on the economic front, U.S. manufacturing growth slipped to 52.1 in April from 54.6 in March, the lowest final reading in six months, according to financial data from Markit. A reading above 50 indicates expansion.
April's Institute of Supply Management report is scheduled to be reported at 10 am ET and will be monitored closely after Tuesday's disappointing Chicago PMI numbers. Economists polled by Reuters predict the increase in manufacturing activity slowed slightly to 51.0 in April, down from 51.3.
Later this afternoon, investors will focus on what the central bank says in its policy statement, and whether it will ramp up its asset-purchase program in light of recent weaker-than-expected economic data. The post-meeting statement is due at 2 pm ET.
"Markets will have to read between the lines as there will not be a Bernanke press conference to follow this time," said Deutsche Bank strategist Jim Reid, in a research note on Wednesday.
"The tone will likely be slightly more dovish given the recent softening in activity and inflation data, but with things not yet weak enough to warrant a change in their policy stance."
At its last meeting in March, the Fed said it would keep its main interest rate at a record low of between zero and 0.25 percent, until the unemployment rate falls below 6.5 percent.
(Read More: Wall Street: Fed Will Print Money Until at Least 2014)
Among earnings, Comcast gained after the cable television provider posted higher quarterly earnings, thanks to strength on the cable side of its business. Comcast is the parent company of NBCUniversal.
Merck declined after the pharmaceutical giant posted weaker-than-expected sales and lowered its full-year profit forecast.
After the closing bell, earnings from Facebook and Visa will be in focus.
To date, a little over 60 percent of S&P 500 companies have posted quarterly results, with 69 percent of firms topping earnings expectations, according to Reuters. If all remaining companies post results inline with estimates, earnings will be up 4 percent on first quarter 2012.
Meanwhile, only 44 percent of companies have beaten revenue forecasts. On average, sales have come in 1 percent below estimates.
Meanwhile, the European Central Bank meets on Thursday, and is widely expected to cut interest rates to give the frail euro zone economy a boost. Most European markets are closed on Wednesday for the May Day public holiday, but London-listed stocks are trading.
"The stock-pickers market will be tested over the coming days. It certainly feels like there is a 'calm before the storm' effect at the moment," wrote Evan Lucas, market strategist at IG, in a note."Macro data has to start showing signs of stabilizing, or central banks have to respond to the data being printed. Without this, a correction is on."
(Read More: Why ECB Rate Cut Could Be Too Little, Too Late)
Weekly mortgage applications gained last week, lifted by demand for refinancings as interest rates slid, according to the Mortgage Bankers Association.