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Background Frailty, a state of vulnerability to stressors resulting from loss of physiological reserve due to multisystemic dysfunction, is common among hospitalized older adults. Hospital clinicians need objective and practical instruments that identify older adults with frailty. The FI‐LAB is based on laboratory values and vital signs and may capture biological changes of frailty that predispose hospitalized older adults to complications. The study's aim was to assess the association of the FI‐LAB versus VA‐FI with hospital and post‐hospital clinical outcomes in older adults. Methods Retrospective cohort study was conducted on Veterans aged ≥60 admitted to a VA hospital. We identified acute hospitalizations January 2011‐December‐2014 with 1‐year follow‐up. A 31‐item FI‐LAB was created from blood laboratory tests and vital signs collected within the first 48 h of admission and scores were categorized as low (<0.25), moderate (0.25–0.40), and high (>0.40). For each FI‐LAB group, we obtained odds ratio (OR) and confidence intervals (CI) for hospital and post‐hospital outcomes using multivariate binomial logistic regression. Additionally, we calculated hazard ratios (HR) and CI for all‐cause in‐hospital mortality comparing the high and moderate FI‐LAB group with the low group. Results Patients were 1407 Veterans, mean age 72.7 (SD = 9.0), 67.8% Caucasian, 96.1% males, 47.0% (n = 661), 41.0% (n = 577), and 12.0% (n = 169) were in the low, moderate, and high FI‐LAB groups, respectively. Moderate and high scores were associated with prolonged LOS, OR:1.62 (95% CI:1.29–2.03); and 3.36 (95% CI:2.27–4.99), ICU admission, OR:1.40 (95% CI:1.03–1.90); and OR:2.00 (95% CI:1.33–3.02), nursing home placement OR:2.36 (95% CI:1.26–4.44); and 5.99 (95% CI:2.83–12.70), 30‐day readmissions OR:1.74 (95% CI:1.20–2.52); and 2.20 (95% CI:1.30–3.74), 30‐day mortality OR: 2.51 (95% CI:1.01–6.23); and 8.97 (95% CI:3.42–23.53), 6‐month mortality OR:3.00 (95% CI:1.90–4.74); and 6.16 (95% CI:3.55–10.71), and 1‐year mortality OR: 2.66 (95% CI:1.87–3.79); and 4.76 (95% CI:3.00–7.54) respectively. The high FI‐LAB group showed higher risk of in‐hospital mortality, HR:18.17 (95% CI:4.01–80.52) with an area‐under‐the‐curve of 0.843 (95% CI:0.75–0.93). Conclusions High and moderate FI‐LAB scores were associated with worse in‐hospital and post‐hospital outcomes. The FI‐LAB may identify hospitalized older patients with frailty at higher risk and assist clinicians in implementing strategies to improve outcomes.