A longitudinal prospective study was conducted at an AIDS designated hospital in Taiwan. The study aimed to determine the incidence of syphilis and to identify risk factors predicting new onset syphilis and relapse into risky behaviors among 117 patients enrolled in the HIV case management program for 1?year. Having a new episode of syphilis was defined as patients had a fourfold increase of serum rapid plasma reagin titers from baseline to 12-month follow-up. After enrollment, 17% relapsed in unprotected sexual intercourse. New onset syphilis was noted in ten (10.4%) participants, and all were men having sex with men. The incidence of syphilis was 5.8 per 100 person-years. Predictors of a new episode of syphilis were higher CD4 cell counts [hazard ratio (HR), 1.003; 95% confidence interval (CI), 1.00-1.006], and recreational drug use (HR, 18.89; 95% CI, 2.78-128.15). Regular screening for syphilis among patients retaining in HIV care remains necessary.