We examined the effects of religious cognitive-behavioral therapy (RCBT) compared to conventional CBT (CCBT) on purpose in life (PIL) in clients with major depression and chronic illness. Participants were randomized to either RCBT (n=65) or CCBT (n=67) to receive ten 50-min sessions over 12 weeks. PIL was measured at baseline, 12, and 24 weeks. Growth curve models examined the effects of treatment group on trajectory of change in PIL. While no significant difference was found between RCBT and CCBT on PIL trajectories in the overall sample, RCBT was more effective than CCBT on increasing PIL in clients who were highly religious (group by time interaction B=-5.87, SE=2.57, p=0.026, Cohen’s d=0.64). Furthermore, baseline religiosity correlated positively with baseline PIL (r=0.34, p<0.0001) and predicted an increase in PIL over time (B=0.23, SE=0.05, p<0.0001). RCBT does not appear to increase PIL more than CCBT, although this may depend on the religiosity of the client.