The frailty index (FI) uses a deficit accumulation approach to derive a single, comprehensive, and replicable indicator of age-related health status. Yet, many researchers continue to seek a single "frailty biomarker" to facilitate clinical screening. We investigated the prognostic accuracy of 70 individual biomarkers in predicting mortality, comparing each with a composite FI. A total of 29,341 individuals from the comprehensive cohort of the Canadian Longitudinal Study on Aging were included (mean, 59.4 ± 9.9 years; 50.3% female). Twenty-three blood-based biomarkers and 47 test-based biomarkers (e.g., physical, cardiac, cardiology) were examined. Two composite FIs were derived: FI-Blood and FI-Examination. Mortality status was ascertained using provincial vital statistics linkages and contact with next of kin. Areas under the curve were calculated to compare prognostic accuracy across models (i.e., age, sex, biomarker, FI) in predicting mortality. Compared to an age-sex only model, the addition of individual biomarkers demonstrated improved model fit for 24/70 biomarkers (11 blood, 13 test-based). Inclusion of FI-Blood or FI-Examination improved mortality prediction when compared to any of the 70 biomarker-age-sex models. Individual addition of seven biomarkers (walking speed, chair rise, time up and go, pulse, red blood cell distribution width, C-reactive protein, white blood cells) demonstrated an improved fit when added to the age-sex-FI model. FI scores had better mortality risk prediction than any biomarker. Although seven biomarkers demonstrated improved prognostic accuracy when considered alongside an FI score, all biomarkers had worse prognostic accuracy on their own. Rather than a single biomarker test, implementation of routine FI assessment in clinical settings may provide a more accurate and reliable screening tool to identify those at increased risk of adverse outcomes.