ContextResearch on associations between medical student empathy and demographics, academic background and career interest is limited, lacks representative samples and suffers from single institutional features. This study was designed to fill the gap by examining associations between empathy in patient care, and gender, age, race and ethnicity, academic background and career interest in nationwide, multi‐institutional samples of medical students in the United States and to provide more definitive answers regarding the aforementioned associations, with more confidence in the internal and external validity of the findings.MethodsFour nationwide samples participated in this study (n = 10 751). Samples 1, 2, 3 and 4 included 3616 first‐year, 2764 second‐year, 2413 third‐year and 1958 fourth‐year students who completed a web‐based survey at the end of the 2017‐2018 academic year. The survey included questions on demographics, academic background and career interest, the Jefferson Scale of Empathy, and the Infrequency Scale of the Zuckerman‐Kuhlman Personality Questionnaire to control for the effect of ‘good impression’ response bias.ResultsStatistically significant and practically important associations were found between empathy scores and gender (in favour of women), race and ethnicity (in favour of African‐American and Hispanic/Latino/Spanish), academic background (in favour of ‘Social and Behavioural Sciences’ and ‘Arts and Humanities’ in Samples 1 and 2) and career interest (in favour of ‘People‐Oriented’ and ‘Psychiatry’ specialties).ConclusionsSpecial features of this study (eg, nationwide representative samples, use of a validated instrument for measuring empathy in patient care, statistical control for the effect of ‘good impression’ response bias, and consistency of findings in different samples from multiple institutions) provide more definitive answers to the issue of correlates of empathy in medical students and increase our confidence in the validity, reliability and generalisability of the results. Findings have implications for career counselling and targeting students who need more guidance to enhance their empathic orientation.