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Safe and effective use of pre-exposure prophylaxis (PrEP) depends on retention in care after initial engagement.The United States PrEP Demonstration Project offered daily oral tenofovir/emtricitabine to participants in San Francisco, Miami, and Washington, D.C. for 48 weeks from 2012 to 2014.The Demo Project participants' patterns of retention were assigned to 1 of 3 categories: early loss to follow-up (ELTF) within the first 12 weeks of the study, retention throughout the study, or intermittent retention in which missed or delayed visits resulted in gaps in medication availability. For each group, baseline characteristics were tabulated. A two-step multivariable analysis was performed.Overall, 366/554 (66.1%) of enrolled participants were retained for all study visits, 127/554 (22.9%) had intermittent retention, and 61/554 (11.0%) ELTF. In multivariable analysis, Miami compared with San Francisco site was associated with ELTF rather than full retention [aOR 2.84; confidence interval (CI): 1.24 to 6.47] and also with intermittent rather than full retention (aOR 2.70; CI: 1.43 to 5.11). Younger age was associated with ELTF (aOR 1.80 for each 10-year decrement in age; CI: 1.26 to 2.57) and intermittent retention (aOR 1.47; CI: 1.17 to 1.84) compared with full retention. Factors associated with ELTF (but not intermittent retention) compared with full retention were black compared with white (aOR 3.32; CI: 1.09 to 10.16), reporting sex work (aOR 4.67; CI: 1.49 to 14.58), lack of regular employment (aOR 2.53; CI: 1.27 to 5.05), and lack of previous PrEP awareness (aOR 2.01; CI: 1.01 to 3.96).Tailored interventions addressing causes and risk factors for loss from PrEP care may improve retention and consistency of PrEP use.