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Background: Few studies have examined long-term outcomes among persons who initiate preexposure prophylaxis (PrEP) in the South, including PrEP discontinuation and sexually transmitted infection (STI) rates., Methods: Care discontinuation (>6 months without a PrEP appointment) and incident STIs were evaluated for patients at 2 PrEP clinics in Durham, NC. We tested for predictors of discontinuation as a binary variable using logistic regression. Model covariates included age, race/ethnicity, sex, known HIV-positive partner, commercial sex work, men who have sex with men (MSM) versus not MSM, type of insurance, and clinic site. A similar analysis was completed for STI incidence, controlling for days in the study., Results: Among 271 patients, mean age was 33.2 years, 46.9% were Black and 11.1% were Latino, 81.2% were MSM, and 32% were uninsured. Preexposure prophylaxis was discontinued in 47%, and another 11% had intermittent care. Sexually transmitted infection incidence was 45.4/100 person-years, and 5 patients were diagnosed with HIV at baseline or in follow-up. Men who have sex with men were less likely to discontinue PrEP relative to non-MSM (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.10-0.64). Baseline STI was associated with a higher likelihood of incident STI (OR, 8.19; 95% CI, 3.69-19.21), whereas care discontinuation was associated with a lower likelihood of STI (OR, 0.28; 95% CI, 0.11-0.65)., Conclusions: Preexposure prophylaxis programs in the Southern United States are reaching uninsured and predominantly Black and Latino MSM, but discontinuation rates are high despite elevated rates of incident STI and HIV. Further work is required to elucidate causes of PrEP discontinuation and encourage persistence in care., Competing Interests: Conflict of Interest and Sources of Funding: Research reported in this publication was supported by the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases under Award Number K23AI137121 to M.E.C. and by the National Heart, Lung, and Blood Institute under Award Number K23HL137611 to N.L.O. This publication also resulted in part from research supported by the Duke University Center for AIDS Research, an NIH-funded program (5P30 AI064518). M.E.C. reports the following financial disclosures: research grants from Gilead, consulting fees from FHI360, and honoraria from UpToDate. A.C.S. has received honoraria from UpToDate and Hologic Inc, and grants from Gilead FOCUS and the NIH National Institute of Allergy and Infectious Diseases., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)