The effects of religious coping, the potential moderation of such effects by religious affiliation (i.e., Catholic, Protestant), and the potential mediation of such effects by various factors (i.e., cognitive restructuring, social support, perceived control) were investigated in patients and significant others coping with the stress of kidney transplant surgery. At 3 and 12 months after transplantation, results showed that the use of religious coping was generally associated with better adjustment both concurrently and over time in both patients and significant others. These effects were moderated by religious affiliation, such that religious coping was more effective in promoting adjustment for Protestants than for Catholics. Religious coping was related to adjustment beyond the effects of the proposed mediators. Implications of these results for future research and practice are discussed.