Background This study investigates the association between frailty and mortality in Eastern European populations, which remains largely unexplored compared with Western Europe. The aim is to assess the risk of all-cause and cardiovascular mortality associated with varying levels of frailty.Methods A prospective multicentre cohort study was conducted, involving random population samples from the Czech Republic, Poland and Lithuania. The baseline survey (2002-2005) included 26 746 individuals aged 45-69 years, with an average follow-up of 13 years. Frailty was measured using a Comprehensive Geriatric Assessment (CGA)-based Frailty Index (FI), calculating the number of deficits in each domain. Cox proportional regression models and inverse probability weighting (IPW) were employed to account for risk factor differences among the frailty groups: robust, prefrail, mild, moderate and severe.Results The study included 14 287 people, among whom 891 were frail, with a total of 2402 deaths. Compared with non-frail persons, those with mild (IPW HR 2.06, 95% CI 1.60 to 2.66) and severe (IPW HR 2.71, 95% CI 1.45 to 5.07) frailty had more than twofold elevated risk of all-cause mortality. For cardiovascular mortality, the corresponding HRs were (IPW HR 3.05, 95% CI 2.14 to 4.35) and (IPW HR 3.88, 95% CI 1.95 to 7.74). Men exhibited a higher mortality risk at all frailty levels only in unweighted analysis. Country-specific differences were not significant.Results The study included 14 287 people, among whom 891 were frail, with a total of 2402 deaths. Compared with non-frail persons, those with mild (IPW HR 2.06, 95% CI 1.60 to 2.66) and severe (IPW HR 2.71, 95% CI 1.45 to 5.07) frailty had more than twofold elevated risk of all-cause mortality. For cardiovascular mortality, the corresponding HRs were (IPW HR 3.05, 95% CI 2.14 to 4.35) and (IPW HR 3.88, 95% CI 1.95 to 7.74). Men exhibited a higher mortality risk at all frailty levels only in unweighted analysis. Country-specific differences were not significant.Conclusions A CGA-based FI is an independent predictor of all-cause and cardiovascular mortality, with even mild frailty increasing the risk. Implementing frailty assessments can improve health risk prediction in older adults from Eastern Europe.