BACKGROUND: Atrial fibrillation (AF) contributes to a prothrombotic state through platelet activation. It is unclear whether increased platelet aggregability in patients with AF is caused by the underlying cardiovascular condition rather than the arrhythmia per se. We investigated the effect of postoperative atrial fibrillation (POAF) on platelet reactivity after coronary artery bypass grafting (CABG). ----- METHODS: This study is a post hoc analysis from a randomized controlled trial (ClinicalTrials.gov: NCT01159639) based on patients undergoing elective primary CABG. Patients were dichotomized according to POAF. Postoperative platelet function testing with arachidonic acid as the platelet agonist (ASPI test) was used to define high on-aspirin platelet reactivity (HAPR). ΔASPI presented the difference between pre- and postoperative ASPI test values. To account for the isolated effect of POAF on platelet reactivity, a propensity score analysis was applied. ----- RESULTS: Overall incidence of POAF was 23% (92 of 398 patients). HAPR was detected in 54% (214 of 398) of patients. HAPR was more prevalent among patients with POAF when compared with patients without POAF (64.1% versus 50.7%; odds ratio [OR], 1.74; 95% confidence interval [CI], 1.08-2.82; p = 0.023). The propensity score model produced a subcohort of patients that was well balanced for comorbidities. When compared with the matched group without POAF, the POAF group maintained its prevalence for HAPR (64.1% versus 45.7%; OR, 2.13; 95% CI, 1.18-3.85; p = 0.012) and had greater ΔASPI values (15.0 [IQR, 0.0-36.0] vs 8.0 [IQR, -5.5-19.5]; p = 0.030). ----- CONCLUSIONS: The main finding of our study indicates there is added platelet activation in patients with POAF after CABG before and after controlling for pathologic conditions through propensity matching. The present study does not prove a causal association between POAF and HAPR.