BACKGROUND: Although numerous studies have reported on PTSD prevalence in high-risk occupational samples, previous meta-analytic work has been severely limited by the extreme variability in prevalence outcomes. METHODS: The present systematic review and meta-regression examined methodological sources of variability in PTSD outcomes across the literature on high-risk personnel with a specific focus on measurement tool selection. RESULTS: The pooled global prevalence of PTSD in high-risk personnel was 12.1% [6.5%, 23.5%], and was similar to estimates obtained in other meta-analytic work. However, meta-regression revealed that PTSD prevalence differed significantly as a function of measurement tool selection, study inclusion criteria related to previous traumatic exposure, sample size, and study quality. PTSD prevalence estimates also differed significantly by occupational group and over time, as has also been reported in previous work, though exploratory examination of trends in measurement selection across these factors suggests that measurement strategy may partially explain some of these previously reported differences. CONCLUSIONS: Our results highlight a pressing need to better understand the role of measurement strategies and other methodological choices in characterizing variable prevalence outcomes. Understanding the role of methodological variance will be critical for work attempting to reliably characterize prevalence as well as risk and protective factors for PTSD.