Abstract: The goal of this study was to examine the cost-effectiveness of evidence-based psychotherapies for posttraumatic stress disorder (PTSD), including prolonged exposure and cognitive processing therapy, by comparing four delivery modalities: home-based telehealth (patient in home), office-based telehealth (patient in one office, provider in another), in-home in-person, and in-office in-person. Pooled data from 268 veterans enrolled in two harmonized PTSD clinical trials were used to examine costs related to personnel, travel mileage, and office space. Cost-effectiveness was calculated using an incremental cost-effectiveness ratio that included unadjusted medians of cost differences between modalities and percent change in clinical outcomes. K-sample equality of medians tests were used to ascertain statistical significance in differences across treatment modalities for the total cohort, as well as for cohorts based on greater baseline PTSD severity (baseline Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, fifth edition, score ≥39 points), for the half of participants who did not respond as well to therapy, and for those who experienced reliable change in PTSD symptoms. The median incremental cost-effectiveness ratio was -$81 across all treatment modalities, -$92 for in-office in-person, -$92 for home-based telehealth, -$131 for office-based telehealth, and -$55 for in-home in-person. Sensitivity analyses examining baseline PTSD severity and responder status are also presented. Cost-effectiveness differed across treatment modalities, but only for those who were considered treatment responders. Shared decision making can help clinicians determine the best therapy delivery approach for each patient suffering from PTSD.