Ascites after liver transplantation, although uncommon, presents a serious clinical dilemma. The hemodynamic changes that support the development of ascites before liver transplantation are resolved after transplant; therefore, persistent ascites (PA) after liver transplantation is unexpected and poorly characterized. The aim of this study was to define the clinical factors associated with PA after liver transplantation. This was a retrospective case -control analysis of patients who underwent liver transplantation at the University of Pennsylvania. PA occurring for more than 3 months after liver transplantation was confirmed by imaging studies. PA was correlated with multiple recipient and donor variables, including etiology of liver disease, preoperative ascites, prior portosystemic shunt (PS), donor age, and cold ischemic (CI) time. There were 2 groups: group 1, cases with PA transplanted from November 1990 to July 2001, and group 2, consecutive, control subjects who underwent liver transplantation between September 1999 and December 2001. Both groups were followed to censoring, May 2002, or death. Twenty-five from group 1 had ascites after liver transplantation after a median follow-up of 2.6 years. In group 1 vs group 2 (n ؍ 106), there was a male predominance 80% vs 61% (P ؍ .10) with similar age 52 years; chronic hepatitis C virus (HCV) was diagnosed in 88% vs 44% (P < .0001); preoperative ascites and ascites refractory to treatment were more prevalent in group 1 (P ؍ .0004 and P ,20.؍ respectively), and CI was higher in group 1, (8.5 hours vs 6.3 hours, P ؍ .002). Eight of the 25 (group 1) had portal hypertension with median portosystemic gradient 16.5 mm Hg (range, 16 -24). PS was performed in 7 of 25 cases, which resulted in partial resolution of ascites. The development of PA after liver transplantation is multifactorial; HCV, refractory ascites before liver transplantation, and prolonged CI contribute to PA after liver transplantation. (Liver