ObjectivesHandgrip strength and physical activity are commonly used to evaluate physical frailty; however, their distribution varies worldwide. The thresholds that identify frail individuals have been established in high-income countries but not in low-income and middle-income countries. We created two adaptations of physical frailty to study how global versus regional thresholds for handgrip strength and physical activity affect frailty prevalence and its association with mortality in a multinational population.Design, setting and participantsOur sample included 137 499 adults aged 35–70 years (median age: 61 years, 60% women) from Population Urban Rural Epidemiology Studies community-dwelling prospective cohort across 25 countries, covering the following geographical regions: China, South Asia, Southeast Asia, Africa, Russia and Central Asia, North America/Europe, Middle East and South America.Primary and secondary outcome measuresWe measured and compared frailty prevalence and time to all-cause mortality for two adaptations of frailty.ResultsOverall frailty prevalence was 5.6% usingglobal frailtyand 5.8% usingregional frailty. Global frailty prevalence ranged from 2.4% (North America/Europe) to 20.1% (Africa), while regional frailty ranged from 4.1% (Russia/Central Asia) to 8.8% (Middle East). The HRs for all-cause mortality (median follow-up of 9 years) were 2.42 (95% CI: 2.25 to 2.60) and 1.91 (95% CI: 1.77 to 2.06) usingglobal frailtyandregional frailty,respectively, (adjusted for age, sex, education, smoking status, alcohol consumption and morbidity count). Receiver operating characteristic curves for all-cause mortality were generated for both frailty adaptations.Global frailtyyielded an area under the curve of 0.600 (95% CI: 0.594 to 0.606), compared with 0.5933 (95% CI: 0.587 to 5.99) forregional frailty(p=0.0007).ConclusionsGlobal frailtyleads to higher regional variations in estimated frailty prevalence and stronger associations with mortality, as compared with regional frailty. However, both frailty adaptations in isolation are limited in their ability to discriminate between those who will die during 9 years’ follow-up from those who do not.