Objective <p>This single-center retrospective observational cohort study with propensity score adjustment was conducted to investigate the association between perioperative red blood cell (RBC) transfusion and short-term outcomes in patients undergoing isolated coronary artery bypass grafting (CABG).</p> Methods <p>Adult patients who underwent isolated CABG at our center between September 30, 2021 and February 29, 2024 were included. Patients were divided into two groups: those who received RBC transfusion (RBC+ group) and those who did not (RBC- group) perioperatively. Propensity score matching (PSM) was used to minimize the influence of potential confounding factors between groups. The clinical outcomes, including composite infectious complications, composite ischemic events, and in-hospital mortality, were compared between groups.</p> Results <p>Before PSM, 186 patients were included in the RBC+ group and 177 in the RBC− group. The RBC+ group had significantly higher rates of composite infectious complications, composite ischemic events, and in-hospital mortality than the RBC− group (all <i>P</i> &lt; 0.001). After PSM (96 patients in each group), the RBC+ group still had significantly higher rates of composite infectious complications (<i>P</i> = 0.014) and composite ischemic events (<i>P</i> = 0.002) than the RBC− group; however, no statistically significant difference in in-hospital mortality was observed between the two groups (<i>P</i> = 0.155). In the RBC+ group, higher transfusion volumes were associated with a higher incidence of adverse clinical outcomes.</p> Conclusion <p>Perioperative RBC transfusion was associated with a higher incidence of adverse postoperative clinical outcomes in patients undergoing isolated CABG.</p>