To identify the factors that increase risk of metabolic bone disease of prematurity (MBD).A retrospective case-control study of infants born between January 2013-April 2014 with gestation age <30weeks and birth weight <1000g. MBD was defined as serum alkaline phosphatase above 500U/L and characteristic radiographic changes. Information was obtained on the presence of specific comorbidities.Of 76 infants evaluated, 40 met criteria for MBD. Median gestational age was 25weeks in both groups (p=0.512). Median birth weight of infants with MBD was significantly lower than that of controls (560 vs. 765g, p<0.01). Longer period of parenteral nutrition and dexamethasone use was observed in MBD group. Cholestasis was associated with the highest likelihood of MBD (OR 16.6, 95% CI 4.8-56.9). Seizures (OR 5.2, 95% CI 1.3-20.5) and the prolonged use of diuretics (OR 2.6, 95% CI 1.0-7.0) also significantly increased the likelihood of MBD. Only cholestasis remained significant (OR 9.6, 95% CI 2.1-45.3) after multiple regression analysis.Cholestasis is a significant risk factor for the development of MBD. Our future studies will be directed towards determining the causal relationship between cholestasis and MBD.