PRINCIPLES: Neisseria gonorrhoeae (NG) resistant to ciprofloxacin (CR) was documented for the first time in Geneva in 2002 and increased from 7% that year to 47% in 2005. We describe NG cases during this period and compare characteristics of CR and ciprofloxacin susceptible (CS) cases. METHOD: Geneva microbiological laboratories identified NG cases. Antimicrobial susceptibility testing (AST) was performed on a sample of reported cases. The attending physicians completed questionnaires on demographic and epidemiological characteristics. Risk exposures were assessed by comparing CR and CS cases using logistic regression. RESULTS: 238 NG cases were reported. Of 91 on which AST was performed, 23 (25%) were CR; 91% of these were male vs 87% of CS patients. Men having sex with men (MSM) represented 38% of CR cases compared with 31% of CS cases (p>0.05). Among CR cases 65% were Swiss compared with 56% of CS cases. Median age was 35 years for both. Casual sexual contacts were reported for 88% of CR cases and 72% of CS cases (p>0.05). The difference between CR and CS cases in terms of sexual activity outside Switzerland (50% and 19% respectively) remained significant after adjusting for sexual preference and nationality (OR: 7.0, CI 95: 1.99-24.6). CONCLUSION: Although CR infection was more common among Swiss MSM, only sexual activity outside Switzerland was independently associated with CR. Physicians should request AST before treatment and reconsider first-line use of ciprofloxacin. Surveillance of gonococcal antimicrobial resistance is essential in monitoring epidemiologic trends and updating recommendations on first-line treatment.