Background: Syndromic management is an inexpensive and effective method for the treatment of symptomatic sexually transmitted infections (STIs), but its effectiveness as a method of STI control in at-risk populations is questionable. We sought to determine the potential utility of syndromic management as a public health strategy to control STI transmission in high-risk populations in urban Peru. Methodology: We surveyed 3,285 at-risk men and women from three Peruvian cities from 2003-05. Participants were asked about the presence of genital ulcers, discharge, or dysuria in the preceding six months. Participants reporting symptoms were asked about subsequent health-seeking and partner notification behavior. Urine and vaginal swab samples were tested for Neisseria gonorrhoeae and Chlamydia trachomatis by nucleic acid testing. Serum was tested for syphilis and Herpes Simplex Virus-Type 2 antibodies. Findings: Recent urogenital discharge or dysuria was reported by 42.1% of participants with gonorrhea or chlamydia versus 28.3% of participants without infection. Genital ulceration was reported by 6.2% of participants with, and 7.4% of participants without, recent syphilis. Many participants reporting symptoms continued sexual activity while symptomatic, and approximately half of all symptomatic participants sought treatment. The positive and negative predictive values of urogenital discharge or genital ulcer disease in detecting STIs that are common in the study population were 14.4% and 81.5% for chlamydia in women and 8.3% and 89.5% for syphilis among gay-identified men. Conclusions: In our study, STIs among high-risk men and women in urban Peru were frequently asymptomatic and symptomatic participants often remained sexually active without seeking treatment. Additional research is needed to assess the costs and benefits of targeted, laboratory-based STI screening as part of a comprehensive STI control program in developing countries.