BACKGROUND: To date, there is no effective vaccine or no effective drug for mass chemoprophylaxis against malaria. Thus, proper know-how and use of prevention methods is crucial. This study aims to assess the knowledge and practice of malaria prevention methods among the residents of Arba Minch area, Southern Ethiopia. METHODS: A community-based cross-sectional study that utilized a two-stage sampling was conducted from January 22 to February 1, 2007 on a sample of 454 household heads or their deputies. SPSS 16 for windows was used for data analysis. Chi-square and Fisher’s exact probability tests were used to assess the association of selected variables with place of residence. RESULTS: Majority (86.8%) of the respondents mentioned fever as a symptom of malaria, and 98.2% of the respondents reported mosquito bite as the cause of malaria. Three hundred and eighty four (84.6%) of the respondents mentioned mosquito nets as protective measures against mosquito bites. The protective measure mostly used by the respondents or other household members in the last 12 months was mosquito net (73.3%) followed by aerosol insecticide (13%) with the former being used more in rural areas and the latter in urban areas. CONCLUSION: The study subjects’ awareness regarding the cause, symptoms and preventive measures of malaria was high. Use of mosquito net as protective measure against mosquito bites in the last 12 months was high. However, use of other preventive measures was low. Behavioral change communication is required to increase the use of other preventive measures along with mosquito nets.