Background: Sickle cell disease (SCD) is a hemoglobinopathy that can cause multiorgan dysfunction. This study assessed the perioperative outcomes of patients undergoing operations for congenital heart disease who had SCD or sickle cell trait (SCT). Methods: We performed a retrospective review of patients with SCD or SCT who had records in The Society of Thoracic Surgeons Congenital Heart Surgery Database between 2014 and 2019. The primary outcome was operative mortality. Secondary outcomes included postoperative complications. One-to-one propensity score matching was performed between the SCD and SCT groups and the control group for further analysis. Results: Our study population consisted of 73, 411, and 36 501 patients in the SCD, SCT, and control groups, respectively. Median (25%-75% interquartile range) age at surgery was 2.8 (0.4-9.7), 0.60 (0.2-3.1), and 0.70 (0.2-6.4) years in the SCD, SCT, and control cohorts, respectively. Operative mortality, surgery duration, cardiopulmonary bypass time, and cross-clamp time were not significantly different among the 3 groups. The SCD group had a higher rate of postsurgical cardiac arrest than its propensity score-matched control group (5.5% vs 0%, P < .05); otherwise, there were no statistically significant differences in the outcomes between the SCD and SCT groups and their respective matched control groups. Conclusions: Operative mortality after cardiothoracic procedures in patients with SCD or SCT appeared similar to our control patients. While these patients may require unique perioperative management, they can undergo cardiac surgery without an observed increase in mortality.