Myelomeningoceles are formed by prenatal failure of neural tube closure and can cause hydrocephalus, motor abnormalities, and developmental delay. Although small defects are amenable to primary closure, larger defects often require complex reconstruction. Our goal was to identify factors associated with postoperative soft tissue complications and develop a systematic approach for myelomeningocele closure.A retrospective review was performed at the Children's Memorial Hermann Hospital from January 2013 to January 2019. Patients were identified using International Classification of Diseases, Ninth Revision/Tenth Revision , codes for myelomeningocele. Cohorts were stratified by reconstruction type and defect location. Primary outcomes were incidence of complications including cerebrospinal fluid leak, superficial and deep infection, and wound dehiscence. In addition, we developed an algorithm to standardize closure approach for patients with myelomeningoceles.A total of 172 patients with myelomeningocele were identified with 73 patients undergoing postnatal repair. Overall, 72% of defects were5 cm. Defects were in the lumbar (9%), sacral (8%), and junctional (83%) regions. Overall, 30.1% patients underwent lumbar myofascial repair with 39.7% requiring fasciocutaneous flaps. Larger defects (5 cm) were more likely to be closed with complex fasciocutaneous flaps (82.8% vs 66.0%, P = 0.11). No significant differences were observed in complication rates.In this series, patients with larger myelomeningoceles appear to benefit from complex flap closure. We propose a 5-layer closure for patients with myelomeningocele including the routine use of a myofascial layer. Cutaneous closure technique should be tailored based on specific defect characteristics as outlined in our algorithm. This approach streamlines myelomeningocele repair while optimizing outcomes and decreasing downstream complications.