OBJECTIVE: To examine the association between baseline suicidality and outcome of major depression in a randomized controlled trial of the pharmacotherapy of psychotic depression and to explore the interaction of suicidality, randomized treatment assignment, and depression outcome. METHODS: This study was a secondary analysis of data from 258 persons aged 18 years or older with DSM-IV-defined major depressive disorder with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo (the Study of the Pharmacotherapy of Psychotic Depression [STOP-PD], which ran from 2002 to 2007). The independent variable was baseline suicidality, defined by 4 groups (suicide attempt in the current episode, active suicidal ideation, passive suicidal ideation, and no suicidality). The outcome variables were change in 16-item Hamilton Depression Rating Scale (HDRS(1)(6)) total score (excluding the suicide item) over time and remission of psychotic depression over time. RESULTS: Suicidality groups did not significantly differ on baseline HDRS(1)(6) total score. Baseline suicidality group was significantly associated with change in HDRS(1)(6) score over time in the sample as a whole (F(3),(1)(3)(9)(4) = 8.17; P < .0001), but was not significantly associated with probability of remission over time. Among participants assigned to olanzapine and placebo, persons with no suicidality had a significantly greater reduction in HDRS(1)(6) total score compared to those with passive suicidal ideation (7.5-point difference in change scores between the 2 groups; 95% CI, 4.3-10.7 t(1)(3)(9)(4) = 4.61, P < .0001), active suicidal ideation (4.4 points; 95% CI, 1.4-7.4; t(1)(3)(9)(4) = 2.85, P = .0176), or suicide attempts (6.1 points; 95% CI, 2.8-9.4; t(1)(3)(9)(4) = 3.66, P = .0015). The 12-week change from baseline in HDRS(1)(6) score for patients with no suicidality was not significantly different between the 2 treatment arms. However, the 12-week HDRS(1)(6) improvement was significantly greater in the olanzapine plus sertraline arm, compared with the olanzapine plus placebo arm, for patients with suicide attempts (8.7-point difference in change scores between the 2 groups; 95% CI, 5.1-12.4; t(1)(3)(9)(4) = 4.75, P < .0001), active suicidal ideation (8.1 points; 95% CI, 4.5-11.7; t(1)(3)(9)(4) = 4.38, P < .0001), or passive suicidal ideation (5.7 points; 95% CI, 2.2-9.2; t(1)(3)(9)(4) = 3.23, P = .0012), respectively. CONCLUSIONS: Baseline suicidality predicted worse acute treatment outcome of psychotic depression. However, participants with suicidality had a better outcome when treated with the combination of olanzapine and sertraline than when treated with olanzapine plus placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00056472.