Background: We previously demonstrated improved depression and survival in advanced cancer patients participating in two palliative care (PC) RCTs: ENABLE II (EII; N=322) compared intervention vs. usual care, and ENABLE III (EIII; N=207) compared immediate vs. delayed intervention. The interventions were identical, except in EIII, the intervention included support for family caregivers and the delayed group began the intervention 12 weeks after enrollment. Both EII and EIII included an in-person PC consultation, weekly phone sessions facilitated by a nurse coach, and monthly follow-up calls. The Center for Epidemiologic Studies-Depression (CES-D) scale was collected at baseline and every 6 weeks until death or study completion. Our aim was to examine the moderating effects of baseline depression on the intervention effect and on survival outcomes in both RCTs. Methods: After combining data from the two RCTs the sample consisted of 529 patients. We conducted Cox proportional hazard analyses to examine the effect of the intervention (as a time-varying covariate) and baseline depression scores on subsequent survival. Results: The intervention significantly reduced mortality risk in this sample (Hazard Ratio [HR]= 0.78, CI: 0.63-0.98, p=.029). Adding baseline CES-D scores and the interaction of the intervention and CES-D scores as predictor variables yielded a significant interaction (HR= 0.97, p =.035) that remained after controlling for cancer type. Following this analysis, patients were classified as clinically depressed (baseline CES-D 16) or not, and Cox analyses were conducted using the intervention as the sole predictor within each depression group. Receiving the intervention significantly reduced mortality risk among clinically depressed patients (HR = 0.65, CI: 0.44-0.95, p =.029), but not among non-depressed patients (HR = 0.89, CI: 0.65-1.21, p >.45). Conclusions: The ENABLE intervention improved survival in this combined sample of advanced cancer patients. The intervention effect on survival was moderated by baseline depression levels, such that patients who were depressed at baseline and received the intervention had a longer survival compared with non-depressed intervention patients.