OBJECTIVES/HYPOTHESIS: The propensity for the development of chronic ear disease in patients with certain congenital syndromes is well described. Little is known about the efficacy of surgery in the management of such patients. This paper will review an institutional experience with the surgical management of chronic ear disease in patients with congenital syndromes or multiple major malformations associated with high rates of ear disease. STUDY DESIGN: Retrospective chart review. METHODS: Charts were reviewed to identify patients diagnosed with either a congenital syndrome or multiple major malformations with a known association with the development of chronic ear disease who underwent ear surgery for chronic ear disease (excluding tympanostomy tube placement). Syndromes encountered, surgeries performed, operative outcomes, complications, and the efficacy of ossicular chain reconstruction is reported. RESULTS: Forty-three patients with 14 different syndromes or malformations were identified. These patients underwent 66 surgical procedures on 56 ears. Seventy-nine percent of patients had undergone an ear procedure prior to presentation. Disease eradication was achieved in 64% of ears with a single procedure, and 89% of ears were controlled with two surgeries or less. Thirty-two percent of surgeries involved a canal wall down procedure, a rate similar to that seen for all patients in our practice over the past decade. When used, ossicular chain reconstruction significantly reduced the air-bone gap, resulting in hearing improvement. Results for patients with Down syndrome, Turner syndrome, and conotruncal cardiac abnormalities are discussed. Only minor complications were encountered. CONCLUSIONS: Syndromic patients and those with a major congenital malformation may present with significant chronic ear disease. Appropriate surgical management can yield successful eradication of disease with low complication rates.