More than a quarter of the human population is likely infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) in highly endemic areas. Preventive chemotherapy is the mainstay of control, but only 4 drugs are available: albendazole, mebendazole, levamisole, and pyrantel pamoate. To assess the efficacy of single-dose oral albendazole, mebendazole, levamisole, and pyrantel pamoate against A lumbricoides, hookworm, and T trichiura infections. A systematic search of PubMed, ISI Web of Science, ScienceDirect, the World Health Organization library database, and the Cochrane Central Register of Controlled Trials (1960 to August 2007). From 168 studies, 20 randomized controlled trials were included. Information on study year and country, sample size, age of study population, mean infection intensity before treatment, diagnostic method used, time between evaluations before and after treatment, cure rate (the percentage of individuals who became helminth egg negative following treatment with an anthelminthic drug), egg reduction rate, adverse events, and trial quality was extracted. Relative risk, including a 95% confidence interval (CI), was used to measure the effect of the drugs on the risk of infection prevalence with a random-effects model. Single-dose oral albendazole, mebendazole, and pyrantel pamoate for infection with A lumbricoides resulted in cure rates of 88% (95% CI, 79%-93%; 557 patients), 95% (95% CI, 91%-97%; 309 patients), and 88% (95% CI, 79%-93%; 131 patients), respectively. Cure rates for infection with T trichiura following treatment with single-dose oral albendazole and mebendazole were 28% (95% CI, 13%-39%; 735 patients) and 36% (95% CI, 16%-51%; 685 patients), respectively. The efficacy of single-dose oral albendazole, mebendazole, and pyrantel pamoate against hookworm infections was 72% (95% CI, 59%-81%; 742 patients), 15% (95% CI, 1%-27%; 853 patients), and 31% (95% CI, 19%-42%; 152 patients), respectively. No pooled relative risks could be calculated for pyrantel pamoate against T trichiura and levamisole for any of the parasites investigated. Single-dose oral albendazole, mebendazole, and pyrantel pamoate show high cure rates against A lumbricoides. For hookworm infection, albendazole was more efficacious than mebendazole and pyrantel pamoate. Treatment of T trichiura with single oral doses of current anthelminthics is unsatisfactory. New anthelminthics are urgently needed.