To provide a descriptive analysis of emergency department (ED) patients with spina bifida, a retrospective chart review was conducted of ED patients with spina bifida. Data describing demographics, chief complaints, diagnostics, diagnoses, and disposition were collected. There were 125 patients with 258 ED visits. The most common presenting complaints included fever (n = 55), vomiting (36), headache (32), abdominal pain (23), and genitourinary symptoms (20). The most common diagnoses included urinary tract infection (n = 55), cellulitis (26), seizure (21), headache (17), dehydration (12), and shunt failure (11). Atypical presentations of conditions commonly associated with spina bifida occurred frequently. Forty-three percent of patients were admitted. In conclusion, spina bifida patients often present with serious illness requiring admission and with complications of their underlying condition. Therefore, atypical presentations of commonly associated conditions must be considered.