BACKGROUND. Frailty is a syndrome characterized by a decreased resistance to stressors, leading to increased vulnerability to adverse outcomes, including mortality. Multi-morbidity refers to the presence of two or more chronic diseases, and is associated with increased risk of adverse health outcomes. Most of the literature in frailty is based on older people (65+ years) living in high income countries. OBJECTIVE. To compare the predictive ability of three frailty indices for all-cause and one-year mortality among high- (HIC), middle- (MIC), and low- income country (LIC) participants; and to assess the mortality risk associated with multi-morbidity. METHODS. Using data from the Prospective Urban and Rural Epidemiological (PURE) study, we developed three indices using different definitions of frailty (one phenotypic frailty index; two cumulative deficit indices). All indices were tested for predictive ability for mortality both individually and with multi-morbidity. RESULTS. Prevalence of phenotypic frailty was greatest in LIC (8%), intermediate in MIC (7%), and lowest in HIC (4%). Multi-morbidity was most prevalent in HIC (20%), intermediate in MIC (15%), and lowest in LIC (13%). Increased frailty was associated with greater mortality risk using all frailty indices (e.g. HR (95% CI) of 2.63 (2.35-2.95) for the phenotypically frail relative to the robust). At each frailty level, mortality risk was higher within one year of baseline measurement than afterwards, and increased if it was accompanied by concurrent multi-morbidity (e.g. HR of phenotypic frailty increases from 2.27 (1.96-2.62) to 5.08 (4.34-5.95) if accompanied by multi-morbidity). CONCLUSION. All frailty indices predicted mortality. This study is unique in evaluating the prognostic ability of frailty indices in middle-aged adults across HIC, MIC, and LICs. / Thesis / Master of Science (MSc)