Background <p>Understanding the prevalence of psychological distress among medical students and its association with intention to practice is crucial for enhancing medical student well-being and mitigating healthcare workforce shortages. This study assessed psychological distress among medical students during medical school in China and its association with their intention to practice, based on a large-scale and multicenter national survey.</p> Methods <p>This multicenter, cross-sectional study evaluated 199,257 medical students from 123 schools across 30 provinces in China in 2021. Psychological distress was assessed using the Chinese version of the 12-item General Health Questionnaire. The primary outcome was: “I want to become a doctor after graduation.” Secondary outcomes included six items identifying students’ self-reported attitudes toward a range of statements related to their perceptions of the medical profession, like “Being a doctor is my ideal career choice.” Multivariate linear regression analyzed the relationship between psychological distress and the intention to practice.</p> Results <p>Among the 199,257 participants, 30,813 (15.5%) medical students reported experiencing psychological distress. Compared with students without psychological distress, those reporting psychological distress had lower intention-to-practice (β, -0.20; 95% CI: -0.21 to -0.19; <i>p</i>&lt;.001). Psychological distress was negatively associated with secondary outcomes; these associations were more pronounced among female students and students in the clinical education phase of undergraduate medical education.</p> Conclusions <p>Psychological distress is negatively associated with intention to practice. Medical schools should implement appropriate measures to alleviate psychological distress among medical students, thereby enhancing their intention to practice.</p>