Study objectives: Controversy persists concerning the potential association between intraoperative use of hetastarch (ie, hydroxyethyl starch [HES]) and postoperative bleeding in patients undergoing surgery. To determine whether intraoperative HES use is associated with an increased risk of postoperative bleeding following coronary artery bypass graft (CABG) surgery. Design: Case-control study. Setting: A large academic medical center in the northeastern United States. Participants: A consecutive sample of 238 patients undergoing CABG surgery. Main outcome measures: Cases consisted of patients who had received either greater than or equal to 3 U packed RBCs, greater than or equal to 3 U platelets, greater than or equal to 3 U fresh frozen plasma, or any cryoprecipitate within 72 h after undergoing a CABG procedure, or who had undergone surgical revision for bleeding. All other CABG surgery patients served as control subjects. Results: In multivariate models that controlled for a wide variety of demographic and clinical characteristics, we found that, compared to patients who did not receive any HES during surgery, those who received 1 U intraoperative HES had more than twice the risk of a bleeding outcome (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.10 to 4.91), and those who received 2 or 3 U HES had more than four times the risk of postoperative bleeding (OR, 4.57; 95% CI, 1.74 to 12.00). Conclusions: HES use in patients undergoing CABG surgery may be associated with a significant risk of postoperative bleeding. A double-blinded, randomized, controlled trial will be necessary to confirm this finding.