BackgroundThe prevalence of medical students’ mental distress is high. While schools apply various methods to select a well-performing and diverse student population, little is known about the association between different selection methods and the well-being of these students during medical school. The present retrospective multi-cohort study assessed whether students selected by high grades, assessment, or weighted lottery showed different stress perception levels in Year-1 of medical school.MethodsOf 1144 Dutch Year-1 medical students, 650 (57%) of the cohorts 2013, 2014, and 2018 who were selected by high grades, assessment, or weighted lottery completed a stress perception questionnaire (PSS-14). A multilevel regression analysis assessed the association between selection method (independent variable) and stress perception levels (dependent variable) while controlling for gender and cohort. In a post-hoc analysis, academic performance (optimalvs.non-optimal) was included in the multilevel model.ResultsStudents selected by assessment (B = 2.25,p< .01, effect size (ES) = small) or weighted lottery (B = 3.95,p< .01, ES = medium) had higher stress perception levels than students selected by high grades. Extending the regression model with optimal academic performance (B=-4.38,p< .001, ES = medium), eliminated the statistically significant difference in stress perception between assessment and high grades and reduced the difference between weighted lottery and high grades from 3.95 to 2.45 (B = 2.45,p< .05, ES = small).ConclusionsSelection methods intended to create a diverse student population – assessment and lottery - are associated with higher stress perception levels in Year-1 of medical school. These findings offer medical schools insights into fulfilling their responsibility to take care of their students’ well-being.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12909-023-04411-0.