WBS is a rare disorder caused by mutations in the chromosomal sub-band 7q11.23 involving the elastin gene. The clinical features (craniofacial, developmental, and cardiovascular abnormalities) are variable. The association with cardiac anomalies is a well-recognized feature, and SVAS is the most common cardiac defect found. End-stage ischemic heart disease is unusual in this setting but when it occurs, OHT remains the final therapeutic option. This decision can be difficult to determine, and it must be tailored to the individual patient based on the clinical status and concomitant cardiovascular and multisystem lesions. To date, no cases of OHT in patients with WBS have been described. We present a 14-month-old patient with WBS who developed severe LV dysfunction secondary to ischemia following a complex staged surgery for SVAS repair. He underwent successful OHT with no post-operative complications, and at three-month follow-up, he remains asymptomatic on standard immunosuppressive therapy. This case constitutes the first demonstration that OHT may be indicated for extended survival in selected children with WBS and we discuss the basic principles for extending the indication for OHT to this scenario as well as the particularities for post-transplant care.