We compared the effectiveness of religiously integrated cognitive–behavioral therapy (RCBT) versus conventional CBT (CCBT) on decreasing suicidal thoughts in persons with major depressive disorder (MDD) and chronic medical illness (CMI). Persons ages 18–85 with MDD in the setting of CMI were randomized to either CCBT (n = 67) or RCBT (n = 65) to receive 10 50-min sessions over 12 weeks. Suicidal thoughts were assessed by 3 different measures and a combined measure at baseline, 4, 8, 12, and 24 weeks. Religiosity was assessed at baseline. Mixed effects growth curve models were used to compare the effects of treatment group on change in suicidal thoughts during treatment and 3 months afterward. No differences were found between treatment groups in the intention-to-treat (ITT) analysis. Secondary analyses also indicated no difference between groups. CCBT tended to be more effective than RCBT in reducing suicidal thoughts during the trial (group by time interaction B = −0.175, SE = 0.124, t(246) = −1.41, p = .16) for the combined measure of suicidal thoughts in the ITT analysis, especially in those with low religiosity (B = −0.382, SE = 0.174, t(159) = −2.14, p = .03). Baseline religiosity predicted a decline in suicidal thoughts over time independent of treatment group (B = −0.014, SE = 0.007, t(246) = −1.95, p = .05). CCBT and RCBT are equally effective in decreasing suicidal thoughts. Religiosity predicts a decrease in suicidal thoughts independent of treatment group.