Abstract Background: Defensive medicine prompts physicians not to admit high-risk patients who need intensive care. This phenomenon not only decreases the quality of healthcare services, but also wastes scarce health resources. Defensive medicine occurs in negative and positive forms. Hence, the present study aimed to determine frequency of positive and negative defensive medicine behaviors and their underlying factors among general practitioners in Southeast Iran. Methods: The present cross-sectional study was performed among general practitioners in Southeast Iran. 423 subjects participated in the study on a census basis and a questionnaire was used for data collection. Data analysis was carried out using descriptive and analytical statistics through SPSS 20. Results: The majority of participants were male (58.2%). The mean age of physicians was 40 ± 8.5. The frequency of positive and negative defensive medicine among general practitioners in Southeast Iran was 99.8% and 79.2% respectively. A significant relationship was observed between working experience, being informed of law suits against their colleagues, and committing defensive medicine behavior (P< 0.001). Conclusion: The present study indicated high frequency of defensive medicine behavior in the Southeast Iran. So, it calls policy-makers special attention to improve the status quo