We sought to evaluate the mortality, risk factors for mortality, and resource utilization following cardiac interventions in trisomy 13 (T13) and 18 (T18) children. All T13 and T18 children who underwent a cardiac intervention from January 1999 to March 2015 were identified from the Pediatric Health Information System database. Data collected included demographics, type of congenital heart disease (CHD), cardiac interventions, comorbidities, length of stay (LOS), hospital charges, and deaths (within 30 days). Logistic regression analysis was used to determine factors associated with mortality. There were 49 (47% females) T13 and 140 (67% females) T18 subjects. The two cohorts were similar in distribution for race, geographic region, insurance type, and median household income. The most common CHD in both groups was a shunt lesion followed by conotruncal defects. Compared to T18, the T13 cohort had higher mortality (29% vs. 12%), tracheostomies (12% vs. 4%), gastrostomies (18% vs. 6%), and overall resource use (P < 0.05 for all). White race (OR 0.23, 95% CI 0.06–0.81) in T13 and older age (in weeks) at surgery in T18 (OR 0.75, 95% CI 0.64–0.86) were associated with lower mortality. A select group of T13 and T18 CHD patients can undergo successful cardiac interventions, albeit with a higher mortality and resource use. T13 patients have higher mortality and resource use compared to T18. In T13 and T18 patients, interventions for CHD may be an acceptable and ethical option following a careful individualized selection and counseling by a team of experts.