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Objective: To evaluate whether out-of-pocket (OOP) costs reduced HIV pre-exposure prophylaxis (PrEP) persistence., Data Source: Participants from five urban community health centers (CHCs) in four US cities enrolled in a PrEP demonstration project from September 2014 to August 2017., Study Design: Patients initiating PrEP were followed quarterly until they withdrew from PrEP care or the study ended. Self-reported OOP medication and clinic visit costs were assessed by semiannual questionnaires. Persistence was defined as the time from study enrollment to the last visit after which two subsequent 3-month visits were missed. Multivariable Cox proportional hazard regression was used to assess the effect of demographics, insurance, and OOP costs on PrEP persistence., Principal Findings: Among 918 participants with OOP cost data, the average quarterly OOP cost was $34 (median: $5, IQR: $0-$25). Participants who were men, White, employed, completed college, and had commercial insurance had higher OOP costs. Higher OOP costs were not associated with lower PrEP persistence by Cox proportional hazards regression (adjusted hazard ratio = 1.00 per $50 increase, 95% CI = 0.97, 1.02)., Conclusion: Among patients receiving care from these urban CHCs, OOP costs were low and did not undermine PrEP persistence., (© Health Research and Educational Trust.)