Abstract Background The US Centers for Disease Control and Prevention (CDC) recommends comprehensive sexually transmitted infection (STI) screening every 3–6 months for men who have sex with men (MSM) using human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). The gaps between these recommendations and clinical practice by region have not been quantified. Methods We used survey data collected from the internet-based ARTnet study between 2017 and 2019 on STI screening among MSM across the United States, stratified by current, prior, and never PrEP use. Poisson regression models with robust error variance were used to model factors, including residence in the Southeast, associated with consistent (“always” or “sometimes”) exposure site-specific STI screening during PrEP care. Results Of 3259 HIV-negative MSM, 19% were currently using PrEP, 6% had used PrEP in the past, and 75% had never used PrEP. Among ever PrEP users, 87%, 78%, 57%, and 64% reported consistent screening for STIs by blood sample, urine sample or urethral swab, rectal swab, or pharyngeal swab, respectively, during PrEP care. Compared to PrEP users in all other regions, PrEP users in the Southeast were significantly less likely to be consistently screened for urogenital (adjusted prevalence ratio [aPR], 0.86; 95% confidence interval [CI], .76–.98) and rectal STIs (aPR, 0.76; 95% CI, .62–.93) during PrEP care. Conclusions Substantial gaps exist between CDC recommendations for STI screening during PrEP care and current clinical practice, particularly for rectal and pharyngeal exposure sites that can harbor asymptomatic infections and for MSM in Southeast states where the STI burden is substantial.