The objective of the study was to explore gender differences in the risk factors of non-communicable diseases among medical students in Nepal. We randomly selected two private and one government medical college located in Kathmandu Valley. All the third year medical students (n = 191) from these selected colleges were requested to participate in an anonymous cross sectional survey. We gathered information about different risk factors for non-communicable diseases including smoking and drinking habits, physical activity and fruit and vegetable consumption. We identified significant gender differences in the clustering of modifiable risk factors among our study population (p value = 0.032). Logistic regression model showed that male and female medical students were significantly different in terms of smoking status [aOR = 4.12, 95 % confidence interval (CI) 1.57; 10.85] and high level of physical activity (aOR = 4.50, 95 % CI 1.80; 11.21). Male medical students should be targeted in future behavioral interventions for smoking cessation, while physical activity among female medical students needs to be promoted.