OBJECTIVES:  Ascites is the most common complication of cirrhosis. Large volume paracentesis has become routine treatment for patients with large ascites. Plasma expanders are recommended in large volume paracentesis to prevent circulatory dysfunction. The objective of this analysis was to evaluate the cost-effectiveness of various US plasma expanders, albumin, saline or no fluid, in patients with decompensated cirrhosis and ascites requiring large volume paracentesis. METHODS:  A decision tree cost-effectiveness analysis was developed to evaluate the cost-effectiveness of various treatments for decompensated cirrhosis from a US hospital perspective using a 3 month time horizon. The model comparators included available US treatments: albumin, saline, and no fluid. Costs in the model included pharmacy costs and medical costs for the cirrhosis complications of hyponatremia, renal dysfunction, and hepatic encephalopathy. Effectiveness inputs were literature-based and included mortality as well as the rates of medical complications. QALYs were calculated based on health state utilities for decompensated cirrhosis and encephalopathy. The primary model results were incremental cost-effectiveness ratios (ICERs) for cost per life saved and cost per QALY. RESULTS:  Despite albumin having higher pharmacy costs ($261) than saline ($6) and no treatment ($0), the total cost per patient was lower with albumin ($2,583) than saline ($3,356) and no fluid ($3,907) due to lower medical complication costs with albumin ($2,322) compared to saline ($3,350) and no treatment ($3,907). The results showed that albumin had the highest survival rate (97.9%, 95.7%, and 96.2% for albumin, saline and no fluid) and gained the most QALYs (0.719, 0.698, and 0.701, respectively). In the cost per life saved and cost per QALY analyses, albumin dominated (i.e. more effective and less costly) saline and no fluid alternatives. CONCLUSIONS:  This analysis suggests that albumin is the most cost-effective treatment for patients with decompensated cirrhosis with ascites requiring large volume paracentesis.