BACKGROUND Studies show 11% to 15% of women treated for Chlamydia trachomatis are reinfected 3 to 4 months after treatment, suggesting the need for rescreening. There is little information on infections among men, infections with Neisseria gonorrhoeae or Trichomonas vaginalis, or long-term follow-up. OBJECTIVE To determine the incidence of new sexually transmitted infections during the year after a visit to a sexually transmitted disease (STD) clinic and associated risk factors. DESIGN Secondary analysis of data from a randomized, controlled trial (RESPECT-2). SETTING 3 urban STD clinics. PATIENTS Sexually active patients enrolled in an HIV prevention counseling trial. MEASUREMENTS Patient characteristics at the initial visit; behaviors during follow-up; and new infections with C. trachomatis, N. gonorrhoeae, or T. vaginalis (women only) detected during 4 scheduled return visits and any other interim visits. RESULTS 2419 persons had 8129 three-month follow-up intervals. Among 1236 women, 25.8% had 1 or more new infections (11.9% acquired C. trachomatis, 6.3% acquired N. gonorrhoeae, and 12.8% acquired T. vaginalis); among 1183 men, 14.7% had 1 or more new infections (9.4% acquired C. trachomatis, and 7.1% acquired N. gonorrhoeae). Black persons and those with sexually transmitted infections at baseline were at highest risk for recurrent infection (adjusted odds ratio, 2.5 and 2.4, respectively). For persons infected at baseline, the risk for infection was high at 3 and 6 months (16.3 per 100 three-month intervals) and remained high at 9 and 12 months (12.0 per 100 three-month intervals). Most (67.2%) infections were diagnosed during study-related visits, and 66.2% of these patients reported no symptoms. LIMITATIONS Because patients were recruited from STD clinics, results may not be generalizable. CONCLUSIONS Men and women who receive diagnoses of C. trachomatis, N. gonorrhoeae, or T. vaginalis infections should return in 3 months for rescreening because they are at high risk for new asymptomatic sexually transmitted infections. Although single-dose therapy may adequately treat the infection, it often does not adequately treat the patient.