Infants with a single ventricle can develop systemic ventricular dysfunction (SVD) after stage 1 operation, but available information is sparse. We reviewed our patients having Norwood, Sano, or hybrid procedures to better understand this problem. We conducted a retrospective, case-controlled cohort study of 267 patients having stage1 operation, examining outcomes between stages 1 and 2 (survival and subsequent cardiac surgeries), predictor variables, and histology of hearts explanted at transplantation. SVD developed in 32 (12%) patients and resolved in 13 (41%); mean age of onset was 3.0 ± 1.63 months; median = 2.79. SVD was not associated with cardiac anatomy, type of stage 1 procedure, weight, coronary abnormality, or atrioventricular valve regurgitation. The mean age of resolution = 12.1 ± 9.6 months; median = 6.3, and resolution may have been more likely with a systemic LV than RV (p = 0.067). Outcomes for the entire SVD group were less favorable than for those without, but patients with resolution of SVD had outcomes at least as good those without SVD. Myocardial histology (n = 4) suggested chronic ischemia. The risk of SVD after stage 1, while low, may be a fundamental feature of this patient population. SVD occurs with either a systemic RV or LV, although patients with a systemic LV may be more likely to have resolution than those with an RV. We identified no predictor variables, but histologic findings suggest chronic ischemia may be involved. Given the low incidence of SVD, multi-center studies will be required to better define predictors of onset and resolution.