We report on a 16‐year‐old girl with short‐chain L‐3‐hydroxyacyl‐coenzyme A (CoA) dehydrogenase deficiency resulting in juvenile‐onset recurrent myoglobinuria, hypoketotic hypoglycemic encephalopathy, and hypertrophic/dilatative cardiomyopathy. Urinary organic acids showed traces of 3‐hydroxy‐dodecanedioic acids and small amounts of suberic, sebacic, and adipic acids. There was a marked decrease in L‐3‐hydroxyacyl‐CoA dehydrogenase activity in muscle with acetoacetyl‐CoA as substrate (2.48 μmol/min/gm; normal = 6.90 ± 1.80 μmol/min/gm of tissue; n = 11), contrasting with normal L‐3‐hydroxyacyl‐CoA dehydrogenase activity with 3‐ketooctanoyl‐CoA and 3‐ketopalmitoyl‐CoA as substrates. Short‐chain L‐3‐hydroxyacyl‐CoA dehydrogenase activity was normal in fibroblasts, suggesting a tissue‐specific defect.