In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two-and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A singledose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.) S oil-transmitted helminths affect more than two billion people worldwide (1, 2). They are widely endemic in the tropics and are prevalent mostly in preschool and school-age children (3, 4) as well as in pregnant women (5). Infections are related to poor sanitation and hygiene and classified as neglected tropical diseases (6). These infections are responsible for significant morbidity, which includes anemia (7,8), stunting (9), and iron and vitamin A deficiencies (10-13). Additionally, helminth infections have the capacity to reduce the host immune response to vaccines as well as to environmental and parasitic antigens (14-16). The consequences of such hyporesponsiveness may explain changes in host susceptibility to commonly encountered pathogens, as reported recently (17)(18)(19). However, helminths may have beneficial effects as well, such as dampening of excessive inflammatory responses against other pathogens or environmental antigens (14, 20,21). Nevertheless, it is commonly accepted that the risks of helminth infection outweigh the benefits, and several public health interventions are in place to control soil-transmitted helminths.Albendazole is frequently used in mass drug administration (MDA) campaigns as a principal control tool for intestinal helminth infections (2,(22)(23)(24). Howeve...