Background The use of stimulant drugs among students is a prevalent and increasing issue. Psychological factors and personality traits are significant contributors to addictive disorders. 
Objective This study aimed to investigate the prevalence of stimulant abuse among medical students in the general practice program at Guilan University of Medical Sciences, as well as to examine the association between students’ personality traits and stimulant abuse.
Methods This analytical cross-sectional study was conducted on medical students in the general practice program at Guilan University of Medical Sciences between 2022-2023. The demographic information checklist, NEO five-factor inventory (NEO-FFI), and drug abuse screening test (DAST-10) were used. Data were entered into IBM SPSS software, version 26. Data analysis was performed using chi-square, Fisher’s exact, independent t-test, Spearman’s correlation, and logistic regression tests. The significance level was set at 0.05 for all tests.
Results The sample consisted of 232 medical students, of whom 16.8% reported stimulant drug abuse. The intensity of stimulant drug abuse was moderate in 56.4% of the participants. The prevalence of stimulant drug abuse was significantly higher among men, single people, those in the internship period, and those living alone (P<0.05). Also, stimulant drug abuse was significantly related to personality traits of more openness (P=0.008) and less conscientiousness (P=0.003). Based on the results of logistic regression, gender (P=0.004), marital status (P=0.002), place of residence (P=0.006), openness (P=0.009), and conscientiousness (P=0.001) had a significant relationship with stimulant abuse. 
Conclusion The findings of this study, along with previous research, indicate a growing trend of stimulant abuse among medical students. The abuse of stimulant drugs was more common in people with the personality trait of eagerness for new experiences; however, the personality trait of conscientiousness was lower in users.