Objective: In view of the increased prevalence of chloroquine resistance and the recent WHO malaria drug policy recommendation to use a combination of therapies especially artemisinin-based combination therapies (ACTs) in Africa, we tried to assess the prescription pattern and level of knowledge in the use of antimalarial drugs including ACTs among medical practitioners in Osogbo metropolis, southwest Nigeria, an endemic area of Plasmodium falciparum infection. Method: Questionnaires were sent to every medical practitioner working in all the health facilities in the metropolis, namely, a teaching hospital, general hospital, mission hospital, comprehensive health centre and 20 privately owned health facilities. Of the total of 100 questionnaires sent out, 96 were completed and returned while the remaining 4 were not returned. The questionnaires were self-administered. Result: Sixty-seven percent of the respondents work in the teaching hospital, while the remaining 33% either work in the general hospital or in private medical practice. 82.4% prescribed chloroquine despite the widespread resistance, indicating that this remains the most prescribed antimalarial drug. 45.7% apply the dosage regimen correctly (Χ2 P<0.005); 66.7% prefer the use of chloroquine injection; 85.6% give chlorpheniramine with chloroquine because of pruritus; 14.4% give it because of its synergistic and reversal mechanism. Other commonly prescribed drugs include sulphadoxine-pyrimethamine (71.1%), halofantrine (53.6%), amodiaquine and quinine (51.1%), mefloquine (20.6%), artemisinin or ACTs (18.6%) and co-trimoxazole (17.5%). Of these, the dosage regimen was applied correctly for: sulphadoxine-pyrimethamine (30.9%), halofantrine (12.8%), amodiaquine (3.2%), co-trimoxazole (2.1%), ACTs, quinine and artemisinin monotherapy (1.1%). About 40% of practitioners prefer the use of combination therapy in the future. Conclusion: There is an obvious paucity of knowledge on the prescription of antimalarial drugs. The proportion of practitioners anticipating the use of combination therapy in the future indicates that with continued medical education the use of combination therapies especially ACTs will be accepted easily.