Incumbent Democratic Senator Evan Bayh decided in February 2010 to retire instead of seeking a third term shortly after Dan Coats announced his candidacy.

Senate candidates in Indiana were required to have submitted 500 signatures from each of the state's nine congressional districts by February 16, 2010, one day after Bayh announced his retirement.

He called for more disclosure of the meetings lawmakers have with lobbyists, banning congressional staff from lobbying for six years after their congressional jobs, requiring Congress members to put all their investments in blind trusts, more disclosure of Senate candidates' personal financial information, and changes to the U.S. Senate filibuster rules.

He focused on Ellsworth's record of voting in support of the Economic Stimulus Act of 2008, cap and trade legislation, and health care bill.

Coats opinion of the healthcare law was that "the only responsible solution ... is to repeal the Obama-Pelosi-Ellsworth health spending bill and quickly replace it with cost-effective, incremental pieces that will decrease costs, increase coverage and not break the bank.