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Azithromycin and doxycycline are recommended for treatment of genital Chlamydia trachomatis infection. A systematic review comparing these antibiotics could affect treatment guidelines.The goal was to perform a meta-analysis to evaluate the efficacy and tolerance of azithromycin versus doxycycline for genital chlamydial infection.Studies were identified by searching computerized English-language databases for the period 1975 to August 2001, supplemented by a manual bibliographic search. Criteria for inclusion were (1) randomized trial design; (2) regimens of oral doxycycline (100 mg twice daily for 7 days) and oral azithromycin (1 g once); (3) males >15 years of age and nonpregnant females >15 years of age; (4) and evaluation of microbial cure at follow-up. Data were extracted on diagnostic assay, follow-up time, study design, sponsorship, patients’ characteristics, adverse events, attrition rates, and outcomes.Twelve trials met the inclusion criteria; 1543 patients were evaluated for microbial cure and 2171 for adverse events. Cure rates were 97% for azithromycin and 98% for doxycycline. Adverse events occurred in 25% and 23% of patients treated with azithromycin and doxycycline, respectively. After pooling of the data, differences in efficacy and risk were computed. The efficacy difference for microbial cure (0.01; 95% CI, −0.01–0.02) and the risk difference for adverse events (0.01; 95% CI, −0.02–0.04) between the two drugs were not statistically significant.Azithromycin and doxycycline are equally efficacious in achieving microbial cure and have similar tolerability. Further head-to-head trials comparing these antibiotics are unnecessary.