Objective To investigate the differences in postoperative mortality and identify potential influential factors in patients with a systemic left ventricle (SLV) versus a systemic right ventricle (SRV) following total cavopulmonary connection (TCPC). MethodsWe retrospectively collected data from functional single ventricle patients who underwent TCPC at the Department of Cardiac Surgery, Guangdong Provincial People’s Hospital, between October 2004 and July 2021. The cohort was categorized based on ventricular morphology into two groups: a SLV group and a SRV group. All procedures were performed via a median sternotomy under cardiopulmonary bypass. ResultsA total of 195 patients were included, comprising 108 patients in the SLV group (69 males, 39 females) and 87 in the SRV group (61 males, 26 females). The median age at surgery was 5.7 (IQR, 4.0-11.2) years, and the median body mass index (BMI) was 15.1 (IQR, 13.5-16.2) kg/m2 for the SLV group. For the SRV group, the median age was 5.7 (IQR, 4.1-8.9) years, and the median BMI was 14.7 (IQR, 13.6-15.9) kg/m2. The proportion of patients with situs inversus, heterotaxy syndrome, and moderate or greater atrioventricular valve regurgitation was significantly higher in the SRV group. Patients in the SRV group had a higher rate of fenestration and experienced longer aortic cross-clamp, cardiopulmonary bypass, and operative times, as well as prolonged postoperative hospital stays and chest tube durations. However, there were no statistical differences in early or late mortality between the two groups (P>0.05). Multivariate analysis identified pulmonary vascular resistance, postoperative aspartate aminotransferase, and postoperative creatinine as independent risk factors for mortality, while postoperative percutaneous oxygen saturation and hemoglobin levels were identified as protective factors. Conclusion The post-TCPC survival rate in patients with a SRV is non-inferior to that in patients with a SLV. However, the overall long-term mortality for both groups remains high, warranting close monitoring of the long-term survival outcomes in this patient population.