<b><i>Introduction:</i></b> Comparative risk assessments (CRAs) for alcohol use are based on indirect estimates of attributable harm, and usually combine country-specific exposure estimates and global risk relations derived from meta-analyses. CRAs for Eastern European countries, such as Lithuania, base their risk relations not on global risk relations, but on a large Russian cohort study. The availability of a direct estimate of alcohol-attributable mortality following the 2017 implementation of a large increase in alcohol excise taxes in Lithuania has allowed a comparison of these indirect estimates with a country-specific gold standard. <b><i>Methods:</i></b> A statistical modelling study compared direct (predictions based on a time-series methodology) and indirect (predictions based on an attributable-fraction methodology) estimates of alcohol-attributable mortality before and after a large increase in alcohol excise taxes in Lithuania. Specifically, Russia-specific versus global relative risks were compared against the gold standard of time-series based predictions. <b><i>Results:</i></b> Compared to direct estimates, indirect estimates markedly underestimated the reduction of alcohol-attributable mortality 12 months post intervention by at least 63%. While both of the indirect estimates differed markedly from the direct estimates, the Russia-specific estimates were closer to the direct estimates, primarily due to higher estimates for alcohol-attributable cardiovascular mortality. <b><i>Discussion:</i></b> As all indirect estimates were markedly lower than direct estimates, current overall relative risks and price elasticities should be re-evaluated. In particular, global estimates should be replaced by new regional estimates based on cohort studies.