Although different cognitive behavioral therapies (CBT) have strong research support for treatment of adult post-traumatic stress disorder (PTSD) more knowledge is needed about the performance of CBT in routine clinical care. The present study is a systematic review and meta-analysis of CBT for PTSD in adults treated in routine clinical care. Ovid MEDLINE, Embase OVID, and PsycINFO were systematically searched for studies published until the end of May 2022. The effectiveness of CBT, methodological quality, and moderators of treatment outcome were examined, and benchmarked by meta-analytically comparing with efficacy studies for PTSD. Thirty-three studies, comprising 6482 participants, were included. The within-group effect sizes (ES) for PTSD-severity at post-treatment (1.75), and follow-up (1.70), on average 6 months post-treatment, were large. The effectiveness studies had very similar ESs as efficacy studies at post-treatment (1.75 vs. 1.72) and follow-up (1.70 vs. 2.02), based on the benchmarking analysis. As the heterogeneity was large, we can only cautiously consider CBT for PTSD an effective treatment when delivered in routine clinical care. The outcomes of effectiveness studies for PTSD seem to be comparable to the results obtained in efficacy studies.