Posttraumatic stress disorder (PTSD) is a severe condition that is associated with trauma-related guilt. We aimed at providing a comprehensive quantitative systematic review on the relationship between trauma-related guilt and adult PTSD. Database searches in Medline, PsycINFO, PTSDpubs and Web of Knowledge resulted in the inclusion of 163 eligible studies with a total of 35 020 trauma survivors. The studies reported on 157 cross-sectional and 19 longitudinal data points. Overall, we included 135 studies not included in previous meta-analyses. Random-effect models yielded a moderate cross-sectional correlation (r = 0.38, 95% CI 0.35–0.42, p < 0.001, I2 = 90.3%) and a small to moderate predictive correlation (r = 0.21, 95% CI 0.13–0.29, p < 0.001, I2 = 66.7%). The association appeared to be stable over time and was robust to sensitivity analyses. All symptom clusters significantly correlated with guilt. No effects were found for military v. civilian populations or clinical v. non-clinical samples. Effects were smaller for high-quality studies and larger for instruments based on DSM-5. Further significant moderators were type of guilt measure and trauma type. The largest association was found among participants reporting war-related trauma (r = 0.44, 95% CI 0.36–0.51) and the smallest among survivors of motor-vehicle accidents (r = 0.18, 95% CI 0.02–0.33). The results underpin the role of trauma-related guilt in the onset and maintenance of PTSD symptoms, which have important clinical implications. Future studies should further explore the change interactions of guilt and PTSD symptoms.