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Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention intervention; however, most studies of PrEP adherence and persistence among men who have sex with men (MSM) have been conducted with MSM who live in urban areas. The experiences of PrEP-using MSM in non-urban areas might differ due to increased barriers to culturally competent care. We examined similarities and differences among urban and non-urban PrEP-using MSM in the southern United States, the region with the highest number of annual HIV diagnoses. We surveyed a total of 78 ( n  = 25 non-urban,  n  = 53 urban) PrEP-using MSM. Self-reported adherence was high across all participants. No differences were observed with respect to PrEP persistence, source of PrEP, or reasons for PrEP initiation. Fewer non-urban than urban men reported STI testing in the past 12 months. Overall, we observed few differences comparing urban and non-urban PrEP-using MSM. Additional studies are needed to describe differences in PrEP initiation comparing urban and non-urban MSM.

Demographic and behavioral characteristics of urban and non-urban PrEP-using MSM in the South