OBJECTIVE: To investigate the impact on sexual behaviour and sexually transmitted infections (STI) of a comprehensive community-led intervention programme for reducing sexual risk among female sex workers (FSW) in Mysore, India. The key programme components were: community mobilization and peer-mediated outreach; increasing access to and utilization of sexual health services; and enhancing the enabling environment to support programme activities. METHODS: Two cross-sectional surveys among random samples of FSW were conducted 30 months apart, in 2004 and 2006. RESULTS: Of over 1000 women who sell sex in Mysore city, 429 participated in the survey at baseline and 425 at follow-up. The median age was 30 years, median duration in sex work 4 years, and the majority were street based (88%). Striking increases in condom use were seen between baseline and follow-up surveys: condom use at last sex with occasional clients was 65% versus 90%, P < 0001; with repeat clients 53% versus 66%, P < 0.001; and with regular partners 7% versus 30%, P < 0.001. STI prevalence declined from baseline to follow-up: syphilis 25% versus 12%, P < 0.001; trichomonas infection 33% versus 14%, P < 0.001; chlamydial infection 11% versus 5%, P = 0.001; gonorrhoea 5% versus 2%, P = 0.03. HIV prevalence remained stable (26% versus 24%), and detuned assay testing suggested a decline in recent HIV infections. CONCLUSION: This comprehensive HIV preventive intervention empowering FSW has resulted in striking increases in reported condom use and a concomitant reduction in the prevalence of curable STI. This model should be replicated in similar urban settings across India.