Background: An association between Transjugular Intrahepatic Porto-Systemic Shunt (TIPS) and the development of hepatocellular carcinoma in patients with cirrhosis has been suggested, but not confirmed. Aim: To evaluate the potential role of TIPS in hepatocellular carcinoma development. Methods: We performed a retrospective case-control study among patients with cirrhosis; all cases had undergone TIPS placement. Cases and controls were followed as outpatients at a single liver care centre in the same timeframe. Results: Overall, 101 patients with cirrhosis (mean age 58 ± 9 years, 64.3% male) were included in each group. Median duration of follow-up was 56.7 months (range 8.2-174.5) for TIPS patients and 67.8 months (range 8.3-183.1) for controls (p = 0.08). In both groups 94% of patients had Child-Pugh Class A or B cirrhosis. The cumulative incidence of hepatocellular carcinoma at 1, 3, 5, and 10 years was 2%, 7%, 18%, and 46% among TIPS patients, and 3%, 10%, 19%, and 39% among controls (log rank test p = 0.19). Compared to controls, hepatocellular carcinoma nodules in TIPS patients were more frequently situated in the right lobe (p