Because numerous papers have demonstrated that depression is associated with worse cardiac prognosis in coronary disease, especially in patients undergoing coronary artery bypass graft (CABG), it is a matter of significant interest whether antidepressant treatment reduces the cardiac risk. Although the proposition remains unproven, the main studies done to date (the SADHART {1} and ENRICHD trials {2}) both suggest that selective serotonin reuptake inhibitors (SSRIs) may reduce cardiac event risk in patients with coronary disease and depression. No similar study has been performed in patients with CABG, and in contrast to the SADHART and ENRICHD signals, this observational study raises the possibility that SSRI treatment, per se, is actually harmful to CABG patients. Since this study is not randomized and lacks any information about the patients’ psychiatric status or subsequent treatment after surgery, one cannot know for certain. If the findings of the paper are true, it remains to be known whether it is due to confounding effects of depression status (i.e. patients on SSRI pre-operatively were individuals with such bad depression that they came to clinical attention, while others with milder or no depression were not treated), due to the SSRIs, or due to some other factor. Hence another study is now urgently needed to replicate and clarify the finding of this paper. The paper is likely to engender controversy because it cuts against the grain of what might have been expected, and because what is missing in its study design is crucial to its proper interpretation in clinical practice. It may heighten resistance in the prescription of SSRIs in coronary artery disease (CAD) patients who may need surgery, although the study results are not really adequate to support such a decision. In the meantime, the clinician must share informed uncertainty with the patient in deciding whether or not to have CABG surgery, and if so whether or not to continue an SSRI antidepressant.