This study tested the efficacy of repeated intravenous psychedelic doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) psychedelic. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard psychedelic dose ameliorated depression measured by the MADRS significantly more than placebo. Psychedelics produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by psychedelic dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of psychedelics on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of psychedelic in PTSD treatment.