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Surgical site infections (SSIs) after colon surgery remain a critical safety issue. Patients with an SSI have an increased risk of death, prolonged hospitalization, and increased costs of care. Red blood cell (RBC) transfusion is given during the perioperative period to increase blood oxygen delivery, but it is associated with complications, including infection. We hypothesized that RBC transfusion would be associated with increased SSI risk in patients undergoing colon resection surgery.A retrospective cohort study was performed using the 2014 National Surgical Quality Improvement Program participant use file. Patients who had colon resection surgery were identified using current procedural terminology codes. The association between perioperative RBC transfusion and superficial and deep incisional SSIs, organ space SSIs, and postoperative septic shock was modeled using logistic regression with propensity score analysis.Of 23,388 patients who had colon resection surgery, 1845 (7.9%) received perioperative RBC transfusion. After controlling for confounders with propensity score analysis and inverse probability of treatment weighting, RBC transfusion had no apparent association with superficial incisional SSI (odds ratio [OR], 1.18; 99% confidence interval [CI], 0.48–2.88) or deep incisional SSI (OR, 1.47; 99% CI, 0.23–9.43). However, RBC transfusion appeared to be associated with increased risk of organ space SSI (OR, 2.93; 99% CI, 1.43–6.01) and septic shock (OR, 9.23; 99% CI, 3.53–24.09).RBC transfusion has no apparent association with increased risk for incisional SSIs, but may be associated with increased risk for organ space SSI and septic shock after colon resection surgery.