BACKGROUND Quinolone-resistant Neisseria gonorrhoeae (QRNG) rates are increasing worldwide. OBJECTIVE (i) To assess the rate of QRNG among patients referred to a venereology clinic in Paris between 2000 and 2004; and (ii) to assess associated epidemiological factors. METHODS Retrospective study of consecutive cases over 2000-2004. Indications and techniques of swabbing and culture were constant over 2000-2004. Susceptibility of N. gonorrhoeae was tested to six antibiotics: ciprofloxacin, amoxicillin, cefotaxime, tetracycline, erythromycin, and spectinomycin. Epidemiological data and anatomical site of N. gonorrhoeae infection were collected. RESULTS Annual numbers of cases decreased (P < 10(-4)) from 2000 (n = 41) to 2002 (n = 12), then increased (P < 10(-4)) in 2004 (n = 60). Anorectal gonorrhoea was more frequent in 2003-2004 (22.0%, n = 18/82) than in 2000-2002 (3.9%, n = 3/76). QRNG rates increased from the period 2000-2002 (1.3%) to 2003 (22.7%, P < 0.01), and 2004 (30.2%, P < 0.005). All QRNG strains had a minimal inhibitory concentration of ciprofloxacin > 1.0 mg/L, thus fitting the international definition of quinolone resistance. There were no significant changes in rates of N. gonorrhoeae resistance to the five other antibiotics. QRNG tended to be more frequent among men who have sex with men (MSM; 16.7% vs. 7.1%), HIV-infected patient (20.5% vs. 11.9%), and patients having more than five partners during the last year (24.4% vs. 17.1%), but statistical significance was not reached in multivariate analyses. CONCLUSIONS We recommend (i) avoiding fluoroquinolones as first-line treatment for N. gonorrhoeae infections in Paris; (ii) that first-line treatment relies on third-generation cephalosporins or spectinomycin; and (iii) reinforcing targeted screening and prevention of gonorrhoea, especially among HIV-positive patients and MSM.