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Regorafenib and nivolumab are drugs approved for second‐line treatment of patients with hepatocellular carcinoma (HCC) after sorafenib failure. However, the effectiveness of regorafenib and nivolumab following sorafenib has not been directly compared. This study retrospectively evaluated 373 patients with HCC who were treated with regorafenib (n = 223) or nivolumab (n = 150) after sorafenib failure between July 2017 and February 2019. Progression‐free survival (PFS; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69‐1.06; P = 0.150), time to progression (TTP; HR, 0.95; 95% CI, 0.77‐1.19; P = 0.680), and overall survival (OS; HR, 0.83; 95% CI, 0.64‐1.07; P = 0.154) did not differ significantly between groups of patients treated with regorafenib and nivolumab, findings consistently observed by multivariable‐adjusted, propensity score‐matched, and inverse probability treatment weighting (IPTW …