Objective To identify small for gestational age (SGA) as an independent risk factor for parenteral nutrition-associated cholestasis (PNAC). Study design In a case-control study, records of infants treated in the neonatal intensive care unit from 1994 through 2003 with gestational ages (GA) < 34 weeks and exposure to parenteral nutrition (PN) >= 7 days were reviewed. The primary outcome was the incidence of cholestasis in infants who were SGA. Secondary outcomes included PN duration, age at full enteral nutrition (FEN) and incidence of late-onset sepsis, necrotizing enterocolitis (NEC) and bronchopulmonary dysplasia (BPD). Analysis was by t test, logistic regression, and chi(2) analysis. Results Cases (n = 79) and control subjects (n = 152) had similar birth weights and GA (963 +/- 465 g versus 1090 463 g; 27 +/- 2 weeks versus 27 +/- 2 weeks; [mean +/- SDI). Of the infants who were SGA, 58% developed cholestasis (OR = 3.3, P <.01). Infants with cholestasis achieved FEN later (43 +/- 25 days versus 23 +/- 11 days) and had higher rates of sepsis (80% versus 340/6), NEC (51% versus 7%), and BPD (65% versus 25%; P <.01). Of infants with cholestasis, infants who were SGA received fewer days of PN than infants who were appropriate for GA (49 +/- 24 days versus 68 +/- 36 days, P =.024). Conclusion Being SGA is an independent risk factor for PNAC. Infants who are SGA require less PN for cholestasis to develop.