Artemisinin-containing antimalarial combination therapies are recommended to confront drug-resistant Plasmodium falciparum malaria. Among the questions surrounding whether these complex multidose treatments will be practical is to what extent patients complete the recommended doses. Combination therapy through coadministration of sulfadoxine-pyrimethamine plus artesunate was introduced as a first-line treatment for uncomplicated malaria in one district in Tanzania. Interventions to optimize correct use were also implemented. We observed 453 patient encounters at one health facility and recorded key practices as health workers dispensed the combination. A total of 253 patients were followed-up at 24 or 48 hours. Complete adherence measured at 48 hours reached 75.0%, based on self-report and tablet counts. This is substantially better than reported elsewhere and compares favorably with intervention studies to optimize adherence to chloroquine. Counseling about what to do if a patient vomits appears to have been an independent risk factor for nonadherence.