Massive post-transplantation ascites is a rare but serious condition following liver transplantation. Although, many etiologies are suggested as the cause of this complication, in some cases the definitive etiology remains unknown. Drug-induced post-transplantation ascites is one of the possible etiologies. In this study we present a case of ascites caused by tacrolimus in the post-liver transplantation period. A 49-year-old man with hepatitis B virus cirrhosis underwent liver transplantation and received tacrolimus, mycophenolate and prednisolone, as the immunosuppressive regimen. Progressive ascites developed after 10 days, in spite of a normal liver function. Various studies, including liver biopsy, were performed but we could not find any etiology for this complication. The tacrolimus was switched to rapamune. Ascites was completely disappeared and up to the last follow-up visit, the patient remained asymptomatic for more than two years. We concluded that after ruling out other etiologies, tacrolimus as a rare cause of post-transplantation ascites should be taken into account. The treatment is discontinuation of the drug.