Posttraumatic stress disorder (PTSD) is a serious mental health condition that affects physical health. However, many military veterans with PTSD refuse or drop out of commonly used trauma-focused, evidence-based treatments. Growing research supports the value of spiritual components in diverse types of health care interventions. This study investigated the effects of the Mantram Repetition Program (MRP) on self-efficacy for managing PTSD symptoms. Outpatient veterans with PTSD (n = 132) were recruited through referrals, and were primarily male (98%), non-Hispanic white (59%) or black (23%), with mean age 58 years (SD = 9). Participants were randomized to case management plus MRP, or to case management alone. MRP participants chose a short, sacred phrase from a spiritual tradition (e.g., “Jesus,” “Barukh attah Adonai,” “Om mani padme hum”), repeating the phrase silently throughout the day to interrupt unwanted thoughts and behaviors, and to improve concentration and attention. Self-efficacy was assessed weekly, and participants were assessed at baseline (Week 1) and postintervention (Week 6) for PTSD symptoms, depressive symptoms, mental health, and spiritual well-being. Results revealed that MRP group self-efficacy means as well as treatment effects showed approximately linear weekly increases from baseline to postintervention. Treatment effects on self-efficacy were significant (p < .01), and mediated treatment effects on depression, mental health, spiritual well-being, satisfaction with physical health, and both self-reported and clinician-assessed PTSD symptoms (all ps < .05). We concluded that MRP fosters self-efficacy for managing PTSD symptoms, favorably affecting diverse facets of well-being, and that physical health effects merit investigation.