It has been shown that medical students have a higher rate of depressive symptoms than the general population and age- and sex-matched peers. This study aimed to estimate the prevalence of depressive symptoms among the medical students of a large school following a traditional curriculum and its relation to personal background variables. A descriptive-analytic, cross-sectional study was conducted in a medical school in Riyadh, Saudi Arabia. The medical students of King Saud University in Riyadh, Saudi Arabia, were screened for depressive symptoms using the 21-item Beck Depression Inventory. A high prevalence of depressive symptoms (48.2%) was found, it was either mild (21%), moderate (17%), or severe (11%). The presence and severity of depressive symptoms had a statistically significant association with early academic years (p < 0.000) and female gender (p < 0.002). The high prevalence of depressive symptoms is an alarming sign and calls for remedial action, particularly for the junior and female students.