Background In Ethiopia, pesticides are widely used for a variety of purposes. The occurrence of contamination and poisoning for farmers is highly reported due to unsafe handling practices and their usage. We assessed knowledge, attitudes and experiences of previous pesticide exposure, and related health problems among farmers who use irrigation in Jimma Zone, Southwest Ethiopia. Methods A community based cross-sectional study was conducted among farmers living in the zone. Respondents were 796 irrigation farmers from 20 kebeles (lowest administration unit) in Jimma Zone. Data were collected using a pretested and structured questionnaire via faceto-face interviews. Both descriptive and inferential statistics analysis were performed. A binary logistic regression was used to identify factors associated with attitudes of farmers towards the safe use of pesticides at P value of ô 0.05 in the final model. Results Among the participants, 54.4% (95%CI, 50.7-58%) knew at least one pesticide control method and 53.7% had positive attitudes towards safe use of pesticide. The mean score of attitudes was found to be 3.9(±0.4). Knowledge including each of the following: the names of the pesticides (AOR, 0.41; 95%CI, 0.25-0.67), methods of pest control and the use of gloves during pesticide exposure (AOR, 1.52; 95%CI, 1.07-2.16) was found to be independent predictor of the farmers' attitudes about safe use of pesticides. Past exposure of pesticide was reported by 89.6% of farmers. Participants reported ingestion (88.9%) and inhalation (90.4%) as possible mechanisms of pesticide exposure. Nearly 42% of farmers had never used any personal protective equipment (PPE) to protect themselves against pesticide exposure. Farmers reported several health complications, which were perceived as complications of pesticide exposure, including: headache, nausea and vomiting, skin rash and irritation and abdominal pain. Conclusions The study exposed the existence of high probability of pesticide exposure, the low safe use of pesticide and the low use of PPE. However, but farmers had positive attitudes towards safe use of pesticides. These findings appeal for the development of effective public health strategies to improve farmers' awareness and safe use of PPE. In addition, there is a need to inform farmers about integrated pest management to prevent severe health complications, which may occur as a result of unsafe and inappropriate use of pesticides.