BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been shown to increase bleeding risks. This study examined the association of perioperative coronary artery bypass grafting (CABG) bleeding risks and SSRI use prior to CABG. HYPOTHESIS: SSRI may be associated with increased bleeding risks after CABG resulting in elevated reoperation rates due to bleeding complications. METHODS: Patients who underwent CABG between 1999 and 2003 (n = 4794) were identified in a tertiary medical center. SSRI use (n = 246) was determined using inpatient pharmacy records. Outcomes included primary end point of reoperation due to bleeding complications and other secondary measures. Multivariate regression models were constructed to adjust for baseline differences between SSRI and control groups. RESULTS: Reoperation due to bleeding complications among SSRI users was not significantly different (odds ratio [OR]: 1.14 (0.52-2.47); P = 0.75) compared to the control group. Other secondary outcomes and 30-day mortality (2.0% in SSRI vs 2.1% in control group; P = 0.92) between the 2 groups were similar. However, the adjusted total volume of postoperative red blood cell (RBC) units transfused was higher in the SSRI group. CONCLUSION: We conclude that there is no compelling evidence to limit the use of SSRIs among patients with coronary artery disease who undergo CABG given the current evidence. Further research may be needed on individual SSRI medications.