Abstract: The study determined the prevalence of malaria in Obafemi Awolowo University community, factors that predispose them to malaria and the rate of drug resistance among subjects in a tertiary institution setting in Ile-Ife, South-Western Nigeria. Blood samples obtained from 316 subjects with febrile condition were screened for malarial parasites using thick and thin films blood smear and thereafter stained with Giemsa and Leishman stains. Microscopy of each slide was also done to determine the degree of parasitemia and types of Plasmodium species. Well structured questionnaires were administered to all subjects. In addition, case files of subjects were examined and reviewed to determine case series of spontaneous report of treatment failures. Subjects were followed-up for 28 days. Treatment outcome was measured by clinical and parasitological recovery after taking the prescribed drug (artesunate + sulfadoxine/pyrimethamine) combination. The subjects’ age range was between 1-63 years mean age of 27.09 (SD = 15.3). The overall prevalence of detection of malaria parasite in the study population was 98.4%. Prevalence rate of malaria in both sexes was insignificant 50.2% in female and 49.8% in male. The prevalence of malaria was highest at age range 16-25 years (54.6%). Symptoms of malaria observed in subjects screened besides fever were headache (68.7%), body pain (40.8%), chills (20%) and vomiting (21.5%). The symptoms resolved proportionally with time and chills and vomiting completely resolved by day 6 in all the subjects and there was total remission of body pain by day 14. Different Plasmodium species namely Plasmodium falciparum, Plasmodium malariae and Plasmodium ovale were observed in the blood samples of the subjects screened. Plasmodium falciparum accounted for the highest prevalence (82.3%) and predominated in the blood samples obtained from children <5 years. Mixed infection with P. falciparum and P. ovale (10.6%), Plasmodium malariae (5.2%) and Plasmodium ovale (1.9%) were prominent in blood samples of adults >15 years of age subjects. Eighty-six subjects fulfilled the follow up criteria as follows: 67.4% (n = 58) of subjects had Adequate Clinical and Parasitological Response (ACPR) of 14-28 days after taking artesunate and antimal (sulfadoxine/pyrimethamine) while treatment failure occurred in 32.6% (n = 22) of subjects. The 7% (n = 6) of the total treatment failure recorded in this study was classified as resistance to the drug used since they returned 4-7 days after treatment with fever and presence of parasitaemia in their blood which indicated Early Treatment Failure (ETF). The remaining 25.6% returned between 7-28 days suggesting recrudescence or re-infection. The high rate of artesunate + sulfadoxine/ pyrimethamine resistance (32.6%) recorded in this study suggests its in-effectiveness in the treatment of uncomplicated malaria infection which is of epidemiological importance in the management of malaria in this community.