BACKGROUND: Intercessory prayer is widely believed to influence recovery from illness, but claims of benefits are not supported by well-controlled clinical trials. Prior studies have not addressed whether prayer itself or knowledge/certainty that prayer is being provided may influence outcome. We evaluated whether (1) receiving intercessory prayer or (2) being certain of receiving intercessory prayer was associated with uncomplicated recovery after coronary artery bypass graft (CABG) surgery. METHODS: Patients at 6 US hospitals were randomly assigned to 1 of 3 groups: 604 received intercessory prayer after being informed that they may or may not receive prayer; 597 did not receive intercessory prayer also after being informed that they may or may not receive prayer; and 601 received intercessory prayer after being informed they would receive prayer. Intercessory prayer was provided for 14 days, starting the night before CABG. The primary outcome was presence of any complication within 30 days of CABG. Secondary outcomes were any major event and mortality. RESULTS: In the 2 groups uncertain about receiving intercessory prayer, complications occurred in 52% (315/604) of patients who received intercessory prayer versus 51% (304/597) of those who did not (relative risk 1.02, 95% CI 0.92-1.15). Complications occurred in 59% (352/601) of patients certain of receiving intercessory prayer compared with the 52% (315/604) of those uncertain of receiving intercessory prayer (relative risk 1.14, 95% CI 1.02-1.28). Major events and 30-day mortality were similar across the 3 groups. CONCLUSIONS: Intercessory prayer itself had no effect on complication-free recovery from CABG, but certainty of receiving intercessory prayer was associated with a higher incidence of complications.