Background: Stress is an essential determinant of depression, leading to a greater prevalence of depression among medical students than the general population; a vulnerable subgroup. The objective of the present study was to determine the prevalence of depression among undergraduate medical students. The study also assessed the demographic, academic, medical and psychosocial factors which may contribute to various degrees of depression in medical students belonging to different academic years. Methods: This was an analytical cross-sectional study conducted among medical college students in Salem, Tamil Nadu between October 2021, and December 2022. Beck’s Depression Inventory (BDI), a validated screening tool for depression was used to identify students who may be experiencing depression. Results: The prevalence of depression among undergraduate medial students was 27.0%; 10.2% had mild depression, 5.4% had borderline clinical depression, 8.5% had moderate depression, 2.4% had severe depression, and 0.5% had extreme depression. Multivariate logistic regression analysis showed that presence of separated or divorced or single parent (AOR 87.86, 95% CI 9.82 to 786.04), being in Phase II (AOR 2.81, 95% CI 1.32 to 5.96), without satisfactory academic performance (AOR 3.62, 95% CI 1.97 to 6.65), presence of active or chief complaints (AOR 3.72, 95% CI 1.99 to 6.97), conflicts in the family (AOR 3.07, 95% CI 1.14 to 8.25), and recent failures (AOR 2.60, 95% CI 1.34 to 5.04) among undergraduate medical students were independent predictors of depression in them (p<0.05). Conclusion: It is crucial that medical schools prioritize the mental health of their students and provide appropriate resources and support. This could include access to mental health services including counselling, training in stress management, and coping strategies, assigning personal tutors and initiatives to reduce the stigma associated with mental health issues