Background: Malaria is a major public health problem in worldwide and causes high morbidity and mortality. Studying its prevalence is necessary to implement effective control measures. Therefore, the aim of this study was to determine the prevalence of malaria in Arba Minch hospital, Ethiopia. Method: A cross sectional study was conducted from January to April, 2010. A well designed and structured questionnaire and Laboratory investigation were used to collect data. Data was processed and analyzed with SPSS version16.0. Results: A total of 400 patients clinically suspected to have malaria were examined with overall prevalence of malaria was 7% (28 malaria cases out of 400 patients) of which 18 (64.3%) were positive for Plasmodium falciparum and 7 (25%) for Plasmodium vivax; the remaining 3 (10.7%) showed mixed infections of Plasmodium falciparum and Plasmodium vivax. Males 16 (4%) were more infected than females 12 (3%). Gender had statistically significant association with malaria infection (p