Urinary bladder perforation due to bladder catheterization in neonates is a rare iatrogenic complication. It has been reported secondary to various causes and a variety of surgical settings in neonates. A case of urinary bladder perforation due to catheterization in a premature baby with Down syndrome, who presented with progressive renal failure and mild-to-moderate ascites, is reported. Urinary bladder perforation should be considered in a case of neonatal ascites with renal failure, which is unexplainable by other causes. We recommend that bladder catheterization in a baby with Down syndrome, whose urinary bladder may be at an increased risk for perforation as part of their generalized hypotonia, should be performed cautiously. To our knowledge, this is the first case report of bladder perforation due to urinary bladder catheterization in a case of Down syndrome.