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The purpose of this study was to identify the determinants of adherence to malaria treatment (co-blistered AS-AQ) among health care providers, medicine sellers and patients in the northeastern region of the Democratic Republic of Congo. A cross-sectional study was carried out on health care providers, medicine sellers and patients in 13 health zones between March and June 2009. Only 69% of the cases of uncomplicated malaria were treated with AS-AQ, including 62.3% of cases treated using the correct dosages. The availability of AS-AQ, the intention to prescribe AS-AQ, longer consultations, providing explanations to patients, working in rural areas, training on the new policy, and the availability of treatment guidelines were found to be significantly associated with treatment adherence among health care providers. The limited availability of AS-AQ, the adverse effects of the treatment, the use of low-quality AS-AQ and the availability of cheap illegal antimalarial drugs were the main factors associated with non-adherence. Among patients, non-adherence was related to the perceived adverse effects of malaria treatment. The results suggest that improving the accessibility and quality of AS-AQ and the quality of communication with patients, the provision of appropriate training to healthcare providers, the provision of treatment guidelines and appropriate supervision are needed to promote the use of AS-AQ.