Objectives The aim of the present study was to investigate differences in prevalence, as well as risk and protective factors, for exposure to workplace aggression between male and female clinicians in Australian medical practice settings. Methods In a cross-sectional, self-report study in the third wave of the Medicine in Australia: Balancing Employment and Life survey (2010-11), 16327 medical practitioners were sampled, with 9449 (57.9%) respondents working in clinical practice. Using backward stepwise elimination, parsimonious logistic regression models were developed for exposure to aggression from external (patients, patients' relatives or carers and others) and internal (co-workers) sources in the previous 12 months. Results Overall, greater proportions of female than male clinicians experienced aggression from external (P<0.001) and internal (P<0.01) sources in the previous 12 months. However, when stratified by doctor type, greater proportions of male than female general practitioners (GPs) and GP registrars experienced external aggression (P<0.05), whereas greater proportions of female than male specialists experienced external (P<0.01) and internal (P<0.01) aggression. In logistic regression models, differences were identified in relation to age for males and experience working in medicine for females with external and internal aggression; working in New South Wales (vs Victoria) and internal aggression for females; a poor medical support network and external aggression, and perceived unrealistic patient expectations with internal aggression for males; warning signs in reception and waiting areas with external aggression for males; and optimised patient waiting conditions with external and internal aggression for females. Conclusions Differences in risk and protective factors for exposure to workplace aggression between male and female clinicians, including in relation to state and rural location, need to be considered in the development and implementation of efforts to prevent and minimise workplace aggression in medical practice settings. What is known about the topic? Workplace aggression is prevalent in clinical medical settings, but there are conflicting reports about sex-based differences in the extent of exposure, and little evidence on differences in risk and protective factors for exposure to workplace aggression. What does this paper add? Differences in workplace aggression exposure rates between male and female clinicians are highlighted, including when stratified by doctor type. New evidence is reported on differences and similarities in key personal, professional and work-related factors associated with exposure to external and internal aggression. What are the implications for practitioners? In developing strategies for the prevention and minimisation of workplace aggression, consideration must be given to differences between male and female clinicians, including with regard to personality, age and professional experience, as well as work locations, conditions and settings, as risk or protective factors for exposure to aggression in medical work.