Abstract Background: Most African countries have adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. The World Health Organization now recommends limiting anti-malarial treatment to those with a positive malaria test result. Limited data exist on how these policies have affected ACT prescription practices. Methods: Data were collected from all outpatients presenting to six public health facilities in Uganda as part of a sentinel site malaria surveillance programme. Training in case management, encouragement of laboratory-based diagnosis of malaria, and regular feedback were provided. Data for this report include patients with laboratory confirmed malaria who were prescribed anti-malarial therapy over a two-year period. Patient visits were analysed in two groups: those considered ACT candidates (defined as uncomplicated malaria with no referral for admission in patients = 4 months of age and = 5 kg in weight) and those who may not have been ACT candidates. Associations between variables of interest and failure to prescribe ACT to patients who were ACT candidates were estimated using multivariable logistic regression. Results: A total of 51,355 patient visits were included in the analysis and 46,265 (90.1%) were classified as ACT candidates. In the ACT candidate group, 94.5% were correctly prescribed ACT. Artemether-lumefantrine made up 97.3% of ACT prescribed. There were significant differences across the sites in the proportion of patients for whom there was a failure to prescribe ACT, ranging from 3.0-9.3%. Young children and woman of childbearing age had higher odds of failure to receive an ACT prescription. Among patients who may not have been ACT candidates, the proportion prescribed quinine versus ACT differed based on if the patient had severe malaria or was referred for admission (93.4% vs 6.5%) or was below age or weight cutoffs for ACT (41.4% vs 57.2%). Conclusions: High rates of compliance with recommended ACT use can be achieved in resource-limited settings. The unique health facility-based malaria surveillance system operating at these clinical sites may provide a framework for improving appropriate ACT use at other sites in sub-Saharan Africa.