It is difficult to treat patients with cirrhosis-associated hepatitis C with pegylated interferon (PEG-IFN) and ribavirin because of thrombocytopenia-related hypersplenism. Both safety and clinical efficacy were retrospectively analyzed for patients who underwent a laparoscopic splenectomy (LS) from January 2003 to December 2007. A total of 35 patients with cirrhosis associated with hepatitis C virus had LS for thrombocytopenia before PEG-IFN and ribavirin therapy, and all patients had thrombocytopenia, which was a contraindication for antiviral therapy. The hepatopathy was Child A in 24 patients, Child B in 10 patients, and Child C in one patient. All 35 patients increased platelet count from 48,000 +/- 15,000 to 155,000 +/- 55,000/microl (P < 0.0001) after LS. The median hospital stay and blood loss were 13.0 days (range, 8 to 57 days) and 342.0 mL (range, 5 to 2350 mL). There was no postoperative death. Twenty-nine (83%) patients had PEG-IFN and ribavirin therapy after LS; 18 had complete therapy and 11 had partial therapy. Of these, nine had a sustained virologic response. A laparoscopic splenectomy for patients with cirrhosis associated with hepatitis C virus can be performed safely and allows induction of antiviral treatment.