From 1994 to 1997, the proportion of Neisseria gonorrhoeae highly resistant to ciprofloxacin (MIC >/=4 microg/mL) increased substantially among female sex workers (FSWs) in the Philippines. Among 1499 Filipina FSWs, we evaluated factors associated with gonococcal infection and with gonococcal antimicrobial resistance. By multivariate analysis, gonococcal infection was associated with sex with a new client, self-prescribed prophylactic antimicrobial use, work in a brothel, and inconsistent condom use and was negatively associated with registration status and vaginal hygiene practices. Factors associated with ciprofloxacin-resistant gonococci included: marital status, living alone, duration of sex work, and clinic site. Further, gonococci highly resistant to ciprofloxacin were isolated from 10 (11.5%) of 87 FSWs reporting self-prescribed antimicrobial use versus 44 (3.4%) of 1295 reporting no antimicrobial use (P<.001). Self-prescribed prophylactic antimicrobial use and inconsistent condom use could be important factors in the continued emergence of gonococcal antimicrobial resistance in the Philippines.