This study assessed the ability of the Posttraumatic Stress Disorder (PTSD) Checklist for the DSM-5 to distinguish between caseness and noncaseness for PTSD among South Africans receiving care for HIV. The PCL-5 and the Structured Clinical Interview for DSM-5-Research Version (SCID-RV) module for PTSD were administered to 688 patients receiving antiretroviral therapy (ART) at two HIV care clinics in the greater Cape Town (South Africa) area. In total, nearly half of the sample (n = 324, 47.1%) reported experiencing an index traumatic event, and 101 participants (14.74%, 95% CI [12.17%, 17.62%]) met the diagnostic criteria for PTSD as measured using the SCID-RV. An ROC curve analysis suggested that a PCL-5 cutoff score of 32 yielded optimal sensitivity (0.88) and specificity (0.88), indicating that the measure was successful in determining caseness for PTSD 88% of the time and noncaseness 88% of the time. The AUC was 94.3%, 95% CI [92.6% to 96.1%], indicating high accuracy. The positive predictive value and negative predictive values were 56.3% and 97.7%, respectively, which suggests that the PCL-5 is an effective screening instrument to determine the presence of PTSD among South African ART users. Undetected and, thus, untreated PTSD may reduce quality of life, impede optimal adherence to ART, and increase the likelihood of risk behaviors among individuals living with HIV, contributing to further infections. The PCL-5 may be used for detection, referral, and treatment of PTSD as a way to enhance its management among individuals receiving HIV care.