We assessed the impact of pre-exposure prophylaxis (PrEP) in the context of a community-based HIV program among female sex workers (FSWs) in Kolkata, India. This was an open-label, uncontrolled demonstration trial. HIV seronegative FSWs over 18 years were eligible. Participants were administered daily tenofovir/emtricitabine (TDF-FTC) with follow-up visits at months 1, 3, 6, 9, 12, and 15. Drug adherence was monitored by self-report, and a random subset of participants underwent plasma TDF testing. 843 women were screened and 678 enrolled and started on PrEP. Seventy-nine women (11%) did not complete all scheduled visits: four women died of reasons unrelated to PrEP and 75 withdrew, for a 15-month retention rate of 89%. Self-reported daily adherence was over 70%. Among those tested for TDF, the percentage of women whose level reached ≥40 ng/mL was 65% by their final visit. There were no HIV seroconversions, and no evidence of significant changes in sexual behavior. This study demonstrated the feasibility and effectiveness of PrEP for FSWs in Kolkata, with very high levels of adherence to PrEP and no HIV seroconversions. The integration of PrEP into an existing community-based HIV prevention program ensured community support and facilitated adherence.