<p><b>Background:</b> Upon FDA/EMEA registration for hepatocellular carcinoma (HCC), sorafenib received a broader therapeutic indication than the eligibility criteria of the landmark SHARP trial. This allowed treatment of SHARP non-eligible patients in daily clinical practice.</p> <p><b>Aim:</b> To assess sorafenib efficacy and safety in SHARP eligible and non-eligible patients, and determine the validity of the current therapeutic indication as described by the FDA/EMEA.</p> <p><b>Patients and methods:</b> Consecutive patients treated with sorafenib for advanced HCC at two Dutch tertiary referral centers between 2007 and 2016 were analyzed retrospectively. Primary outcome was overall survival (OS). Secondary outcomes were time to progression (TTP), response rate, adverse events and reasons for discontinuation. Outcomes were compared between SHARP eligible and non-eligible patients.</p> <p><b>Results:</b> One hundred and ninety-three of 257 (75%) patients were SHARP eligible. SHARP eligible patients (9.5 months, 95% CI 7.7–11.3) had a longer median OS than non-eligible patients (5.4 months, 95% CI 3.6–7.1) (log-rank <i>p</i> < .001). SHARP non-eligible patients were more often Child–Pugh B, had higher AST and ALT levels and developed more grade 3–4 liver dysfunction (44 versus 23%, <i>p</i> < .001) during treatment. SHARP ineligibility remained the strongest predictor of OS (HR 1.78, 95% CI 1.32–2.41) and an independent predictor of TTP (HR 1.45, 95% CI 1.05–2.00) in multivariable analysis.</p> <p><b>Conclusions:</b> Landmark trial outcomes of sorafenib for HCC are reproducible in daily practice, provided that the SHARP eligibility criteria are respected. Based on the findings of this and previous studies, sorafenib usage should be restricted to Child–Pugh A patients.</p