Understanding the efficacy of microfilaricidal drugs is important in guiding the global programme for the elimination of lymphatic filariasis as a public-health problem. We did a systematic review of the available literature to determine which currently available drug intervention most effectively decreases circulating Wuchereria bancrofti microfilaria in individuals and populations. 57 randomised studies of drug efficacy were identified. Data were combined and compared using weighted mean effect estimates taking into account the longitudinal nature of the data. Combined treatment with diethylcarbamazine plus ivermectin, diethylcarbamazine plus albendazole, and ivermectin plus albendazole resulted in average microfilarial intensity decreases that were 0.7%, 4.6%, and 12.7% of the pre-treatment values, respectively. Drug combinations containing diethylcarbamazine were the most effective against microfilarial prevalence and intensity relative to single drugs or other combinations. The relative efficacies of drug combinations have not been well documented from existing studies and therefore limit the application of evidenced-based recommendations for chemotherapy-based interventions to control lymphatic filariasis. These results provide valuable estimates of drug effect using existing data, but highlight the need for more comprehensive comparative drug studies.