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Methodological limitations in PrEP implementation studies may explain why PrEP implementation is lagging. This methodological review provides a description and critique of the methods used to identify barriers to PrEP implementation in the United States (2007–18). For each selected article, we provide: (1) research questions; (2) measures; (3) design; (4) sample (size and type); and (5) theoretical orientation. Among 79 articles which identified knowledge, attitudes, and behavioral and social/structural barriers to PrEP implementation, 51 (65%) were quantitative; 25 (32%) qualitative; and 3 (4%) were mixed-methods; overall, just one-half described a conceptual approach. About two-thirds of articles were conducted with patients and one-third with healthcare providers. Our review reveals a paucity of longitudinal, mixed-methods, and ethnographic/observational research and guiding theoretical frameworks; thus, the applicability of results are limited. We recommend that interventions aimed at PrEP implementation address barriers situated at multiple ecological domains, and thus improve PrEP access, uptake, and adherence.