This study assessed the risk of any bleeding abnormalities, including the risk of gastrointestinal bleeding, associated with antidepressant exposure. We used a case-control methodology. Case patients were individuals admitted with a diagnosis of abnormal bleeding. Control subjects were individuals admitted on the same date without evidence of abnormal bleeding. During the study period, 11,025 case patients were admitted for bleeding abnormalities (matched with 21,846 eligible control subjects), and 1008 were admitted for gastrointestinal bleeding (matched with 1990 eligible control subjects). With respect to any bleeding abnormalities, antidepressants as a group were not associated with an increased risk (adjusted odds ratio [OR], 0.99; 95% confidence interval [CI], 0.90-1.08). Similarly, selective serotonin reuptake inhibitors as a group, the group of tricyclic and related antidepressants, and the group of other antidepressants were not associated with an increased risk of bleeding. With respect to gastrointestinal bleeding abnormalities, antidepressants as a group were associated with a modestly increased risk (adjusted OR, 1.34; 95% CI, 1.01-1.80). Whereas the group of tricyclic and related antidepressants was not associated with an increased risk of bleeding, the group of selective serotonin reuptake inhibitors was associated with a nonsignificant trend toward an increased risk of bleeding (adjusted OR, 1.31; 95% CI, 0.91-1.88) and the group of other antidepressants with a statistically significant increase in the risk of bleeding (adjusted OR, 1.74; 95% CI, 1.04-2.93). In a population with a low baseline risk of bleeding, we detected a significant increase in the risk of gastrointestinal bleeding only.