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Causes of major adverse event after systemic-to-pulmonary shunt procedure are usually shunt occlusion or over-shunting. Outcomes categorized on the basis of these causes will be helpful both for quality improvement and prognostication.Retrospective cohort analysis of children who underwent a systemic-to-pulmonary shunt after excluding those who had it for Norwood or Damus-Kaye-Stansel procedure.The Royal Children’s Hospital, Melbourne, VIC, Australia.From 2008 to 2015, 201 children who had a systemic-to-pulmonary shunt were included.Major adverse event is defined as one or more of cardiac arrest, chest reopening, or requirement for extracorporeal membrane oxygenation. Study outcome is a “composite poor outcome,” defined as one or more of acute kidney injury, necrotizing enterocolitis, brain injury, or in-hospital mortality.Median (interquartile range) age was 12 days (6–38 d) and median (interquartile range) time to major adverse event was 5.5 hours (2–17 hr) after admission. Overall, 36 (18%) experienced a major adverse event, and reasons were over-shunting (n = 17), blocked shunt (n = 13), or other (n = 6). Fifteen (88%) in over-shunting group suffered a cardiac arrest compared with two (15%) in the blocked shunt group (p < 0.001). The composite poor outcome was seen in 15 (88%) in over-shunting group, four (31%) in the blocked shunt group, and 56 (34%) in those who did not experience a major adverse event (p < 0.001). By multivariable analysis, predictors for composite poor outcome were major adverse event due to over-shunting (no major adverse event—reference; over-shunting odds ratio, 18.60; 95% CI, 3.87–89.4 and shunt-block odds ratio, 1.57; 95% CI, 0.46–5.35), single ventricle physiology (odds ratio, 4.70; 95% CI, 2.34–9.45), and gestation (odds ratio, 0.84/wk increase; 95% CI, 0.74–0.96).Infants who suffer major adverse event due to over-shunting experience considerably poorer outcomes than those who experience events due to shunt block. A mainly hypoxic event with maintenance of systemic perfusion (as often seen in a blocked shunt) is less likely to result in poorer outcomes than those after a hypoxic-ischemic event (commonly seen in over-shunting).