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Introduction: The objectives of this study are to develop a summary measure of risky sexual practice and examine the factors associated with this among female sex workers (FSWs) in Karnataka, India. Materials and Methods: Data were drawn from special behavioral surveys (SBS) conducted in 2007 among 577 FSWs in two districts of Karnataka, India: Belgaum and Bangalore. FSWs were recruited using the two-stage probability sampling design. FSWs' sexual practice was considered risky if they reported inconsistent condom use with any sexual partner and reported experience of one of the following vulnerabilities to HIV risk: anal sex, alcohol consumption prior to sex and concurrent sexual relationships. Results: About 51% of FSWs had engaged in risky sexual practice. The odds of engaging in risky sex were higher among FSWs who were older (35+ years) than younger (18–25 years) (58% vs. 45%, Adjusted Odds Ratio (AOR): 2.0, 95% confidence interval (CI): 1.2–3.4), who were currently married than never married (61% vs. 51%, AOR: 4.8, 95% CI: 2.5–9.3), who were in sex work for 10+ years than those who were in sex work for less than five years (66% vs. 39%, AOR: 2.6, 95% CI: 1.6–4.2), and who had sex with 3+ clients/day than those who had sex with fewer clients (67% vs. 38%, AOR: 3.7, 95% CI:2.5–5.5). Conclusion: FSWs who are older, currently married, practicing sex work for longer duration and with higher clientele were more likely to engage in risky sexual practices. HIV prevention programs should develop strategies to reach these most-at risk group of FSWs to optimize the effectiveness of such programs. [ABSTRACT FROM AUTHOR]