Background: No Australian study has reported the association between selective-serotonin reuptake inhibitor (SSRI) and serotonin noradrenaline reuptake inhibitor (SNRI) with coronary artery bypass graft (CABG) surgery morbidity and mortality. Methods: 4136 patients underwent CABG surgery between January 1996 and December 2008 and 105 (2.5%) were SSRI/SNRI users. Bleeding events included platelet, fresh frozen plasma and packed red blood cell transfusion, reoperation for bleeding and gastrointestinal bleeding. In-hospital morbidity included renal failure, stroke, ventilation >24. h, deep sternal wound infection, reoperation (any cause), myocardial infarction and mortality. Results: Median follow-up was 4.7. years (interquartile range, 2.3-7.9. years) and there were 727 deaths (17.6% of total). Use of SSRI/SNRI was associated with new requirement for renal dialysis (adjusted OR = 2.18; 95% CI, 1.06-4.45, p= .03) and ventilation >24. h (adjusted OR = 1.69; 95% CI, 1.03-2.78, p= .04). Neither SSRI/SNRI use nor SSRI/SNRI and concomitant anti-platelet medication increased the odds for any bleeding events (all p> .20). No association was evident with all-cause mortality (adjusted hazard ratio = 1.60; 95% CI .59-4.35, p= .36), or cardiac mortality (adjusted hazard ratio = .31; 95% CI, .04-2.26, p= .25). Conclusions: SSRI/SNRI users experienced an increased risk of renal dysfunction and prolonged ventilation, but not bleeding events or long-term mortality after CABG surgery.