The Fed is expected to keep borrowing costs on hold but its economic commentary will be closely scrutinised for hints about future moves.
In Japan, the benchmark Nikkei 225 index closed down 0.8% at 16,974.45.
Shares of Japanese consumer electronics firm Sharp slumped nearly 12% on reports a takeover deal may be delayed.
According to Reuters, Taiwan's Foxconn - also known as Hon Hai Precision - may postpone its $6bn (Â£4.2bn) purchase of Sharp after receiving "new material information" and is requesting more guidance on its latest quarterly performance.
In China, the Shanghai Composite index rose 0.2% to 2,870.43 while Hong Kong's Hang Seng index dropped 0.15% to 20,257.70.
In Australia, the S&P/ASX 200 index ended 0.15% higher at 5,119.03 even though falling iron ore prices dragged on mining shares.
South Korea's Kospi closed up 0.3% at 1,974.90, despite data showing the unemployment rate hit a five-year high.
The rate rose to 4.1% from 3.5% in February, which was higher than economist expectations, due to a contraction in the manufacturing and construction sectors.
However, analysts say most global investors are focusing on the outcome of the Fed's meeting.
"Another hike is sharply at odds with Fed concerns about increased uncertainty around global/China outlook and market turbulence tightening credit conditions," said Vishnu Varathan from Mizuho Bank.
He added that attention was focused on any hints the bank might make about the frequency of interest rate rises this year.

Sam Matthews stunned the home crowd early on from long range, but Aswad Thomas replied quickly for Dover.
The irrepressible Miller then went out on his own at the top of the scoring charts, notching a quick-fire hat-trick. The second was a real highlight as he wormed his way inside from the corner flag before beating Joe Taylor.
Jack Parkinson made it five before half-time from close range. The break helped Braintree steady matters, and Dover's rampant form subsided.
But Miller grabbed his 14th of the season from a free-kick to cap his perfect day.
Reports supplied by the Press Association.
Match ends, Dover Athletic 6, Braintree Town 1.
Second Half ends, Dover Athletic 6, Braintree Town 1.
Substitution, Dover Athletic. Ira Jackson Jr replaces Ricky Modeste.
Substitution, Braintree Town. Joe Maybanks replaces Sam Matthews.
Substitution, Dover Athletic. Mitchell Pinnock replaces Ricky Miller.
Substitution, Dover Athletic. Ayo Obileye replaces Tyrone Sterling.
Jon Ashton (Braintree Town) is shown the yellow card for a bad foul.
Substitution, Braintree Town. Jack Midson replaces Harry Lee.
Sam Matthews (Braintree Town) is shown the yellow card for a bad foul.
Substitution, Braintree Town. Jon Ashton replaces Barney Williams.
Goal!  Dover Athletic 6, Braintree Town 1. Ricky Miller (Dover Athletic).
Second Half begins Dover Athletic 5, Braintree Town 1.
First Half ends, Dover Athletic 5, Braintree Town 1.
Goal!  Dover Athletic 5, Braintree Town 1. Jack Parkinson (Dover Athletic).
Goal!  Dover Athletic 4, Braintree Town 1. Ricky Miller (Dover Athletic).
Goal!  Dover Athletic 3, Braintree Town 1. Ricky Miller (Dover Athletic).
Goal!  Dover Athletic 2, Braintree Town 1. Ricky Miller (Dover Athletic).
Goal!  Dover Athletic 1, Braintree Town 1. Aswad Thomas (Dover Athletic).
Goal!  Dover Athletic 0, Braintree Town 1. Sam Matthews (Braintree Town).
First Half begins.
Lineups are announced and players are warming up.
Asia markets were mixed on Wednesday as investors waited for the outcome of the latest Federal Reserve meeting.
[NEXT_CONCEPT]
Ricky Miller scored four times in Dover's 6-1 win over struggling Braintree at the Crabble Athletic Ground.