BACKGROUND In using regularly collected or existing surveillance data to characterize engagement in human immunodeficiency virus (HIV) services among marginalized populations, differences in sampling methods may produce different pictures of the target population and may therefore result in different priorities for response. OBJECTIVE The objective of this study was to use existing data to evaluate the sample distribution of eight studies of female sex workers (FSW) and men who have sex with men (MSM), who were recruited using different sampling approaches in two locations within Sub-Saharan Africa: Manzini, Swaziland and Yaoundé, Cameroon. METHODS MSM and FSW participants were recruited using either respondent-driven sampling (RDS) or venue-based snowball sampling. Recruitment took place between 2011 and 2016. Participants at each study site were administered a face-to-face survey to assess sociodemographics, along with the prevalence of self-reported HIV status, frequency of HIV testing, stigma, and other HIV-related characteristics. Crude and RDS-adjusted prevalence estimates were calculated. Crude prevalence estimates from the venue-based snowball samples were compared with the overlap of the RDS-adjusted prevalence estimates, between both FSW and MSM in Cameroon and Swaziland. RESULTS RDS samples tended to be younger (MSM aged 18-21 years in Swaziland: 47.6% [139/310] in RDS vs 24.3% [42/173] in Snowball, in Cameroon: 47.9% [99/306] in RDS vs 20.1% [52/259] in Snowball; FSW aged 18-21 years in Swaziland 42.5% [82/325] in RDS vs 8.0% [20/249] in Snowball; in Cameroon 15.6% [75/576] in RDS vs 8.1% [25/306] in Snowball). They were less educated (MSM: primary school completed or less in Swaziland 42.6% [109/310] in RDS vs 4.0% [7/173] in Snowball, in Cameroon 46.2% [138/306] in RDS vs 14.3% [37/259] in Snowball; FSW: primary school completed or less in Swaziland 86.6% [281/325] in RDS vs 23.9% [59/247] in Snowball, in Cameroon 87.4% [520/576] in RDS vs 77.5% [238/307] in Snowball) than the snowball samples. In addition, RDS samples indicated lower exposure to HIV prevention information, less knowledge about HIV prevention, limited access to HIV prevention tools such as condoms, and less-reported frequency of sexually transmitted infections (STI) and HIV testing as compared with the venue-based samples. Findings pertaining to the level of disclosure of sexual practices and sexual practice-related stigma were mixed. CONCLUSIONS Samples generated by RDS and venue-based snowball sampling produced significantly different prevalence estimates of several important characteristics. These findings are tempered by limitations to the application of both approaches in practice. Ultimately, these findings provide further context for understanding existing surveillance data and how differences in methods of sampling can influence both the type of individuals captured and whether or not these individuals are representative of the larger target population. These data highlight the need to consider how program coverage estimates of marginalized populations are determined when characterizing the level of unmet need.