OBJECTIVES: Hepatocellular carcinoma (HCC) surveillance with biannual ultrasound is currently recommended for all patients with cirrhosis. However, clinical implementation of this “one-size-fits-all” approach is challenging as evidenced by its low application rate. We aimed to evaluate the cost-effectiveness of risk-stratified HCC surveillance strategies in patients with cirrhosis. METHODS: A Markov decision-analytic modeling was performed to simulate a cohort of 50-year-old subjects with compensated cirrhosis. Risk-stratified HCC surveillance strategies was implemented, in which patients were stratified into high-, intermediate-, or low-risk groups by HCC risk biomarker–based scores and assigned to surveillance modalities tailored to HCC risk (2 non-risk-stratified and 14 risk-stratified strategies) and compared with non-stratified biannual ultrasound. RESULTS: Quality-adjusted life expectancy gains for biannual ultrasound in all patients and risk-stratified strategies compared with no surveillance were 1.3 and 0.9–2.1 years, respectively. Compared with the current standard of biannual ultrasound in all cirrhosis patients, risk-stratified strategies applying magnetic resonance imaging (MRI) and/or ultrasound only in high- and intermediate-risk patients, without screening in low-risk patients, were cost-effective. Abbreviated MRI (AMRI) for high- and intermediate-risk patients had the lowest incremental cost-effectiveness ratio (ICER) of $2,100 per quality-adjusted life year gained. AMRI in intermediate- and high-risk patients had ICERs o$3,000 across a wide range of HCC incidences. CONCLUSIONS: Risk-stratified HCC surveillance strategies targeting high- and intermediate-risk patients with cirrhosis are cost-effective and outperform the currently recommended non-stratified biannual ultrasound in all patients with cirrhosis.