Malaria is a serious public health problem particularly in Africa. Over the years, the situation has worsened because of the development of drug resistance to many of the previously efficacious and affordable antimalarial drugs. Following the emergence of chloroquine resistance, Ghana changed her antimalarial drug policy in 2005 opting for artesunate-amodiaquine combination as first line treatment for uncomplicated malaria. Following the implementation of the new policy, there have been several complaints of various side effects. This study was done to determine the level of adherence to the combination therapy and to identify the various factors militating against it so as to provide the basis for intervention.It was a cross sectional study. Patients who reported to any of the district health facilities and were diagnosed as having malaria and put on artesunate-amodiaquine combination therapy were selected by convenience sampling. Their addresses were obtained from their medical records. They were traced to their homes on the fourth day of treatment and the remaining tablets were counted and semi-structured questionnaires administered to them to collect data on various issues on adherence.Data was analyzed using Epi-Info version 3.3.2; 2005. Simple proportions, odds ratios and P-values were calculated.In total, 326 subjects were studied. It was found that only 154(47.2%) adhered to the treatment. One hundred and ten (33.3%) of the 326 participants did not adhere because of side effects. Side effects were significant reasons for non-adherence (P<0.05)The following health system related factors were associated with improved adherence: instructed to take drugs after meals (P=0.05), telling patients the names of the drugs (P <0.05); advised tosleep under insecticide treated bednet (P<0.05). Prescribing other drugs concurrently with the combination therapy was associated with non-adherence (P<0.05)The conclusions were that the proportion of patients who adhere to the combination therapy is low; that side effect is the major reason for non-adherence; service provider factors such as inadequate counseling of patients plays an important role in non-adherence.The recommendations are that public health education on the need to adhere to the combination therapy be intensified; health care providers be retrained to provide adequate and appropriate information; prescribers should avoid polypharmacy. Finally, more of these studies should be conducted in other districts to provide information on the national situation of adherence in the country


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