Background: Excessive smartphone use is common among university students and can negatively affect students’ mental health, but data from Middle-East countries is scarce. Objective of the study was to determine the characteristics of medical students affected by and the prevalence of problematic smartphone use in a sample of Iranian medical students. Methods: This cross-sectional study was conducted in a large Iranian medical university. A convenience sample of 356 students of different years of medical training were recruited. Data on socio-demographic characteristics, daily estimated average time using a smartphone, and main motivations to use a smartphone were collected through a self-reported questionnaire. Problematic smartphone use (PSU) was evaluated using the smartphone addiction scale – short version (SAS-SV) questionnaire. Backward logistic regression analysis was used to understand independent factors associated with PSU. Results: Overall, two-thirds of Iranian medical students were affected by PSU, including 68.5% of male and 64% of female students. Students who lived alone had significantly higher SAS-SV scores than those who lived with their families (p=0.007). Additionally, students with daily smartphone use >4 hours were 3.2 times more likely to be diagnosed with PSU (p<0.001). Social media use was the main motivation that strongly predicted the presence of PSU among medical students (adjusted OR: 2.87, 95% CI: 1.68-4.89). Conclusions: Main motivation to use and duration of phone use are the most important factors predicting problematic smartphone use among medical students.