The purpose of this study was to evaluate the ability of the Pathologic Fracture Mortality Index (PFMI) to predict the risk of 30-day morbidity after pathologic fracture fixation and compare its efficacy with those of the American Society of Anesthesiologists (ASA) physical status, modified Charlson Comorbidity Index (mCCI), and modified frailty index (mFI-5). Cohorts of 1,723 patients in the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2020 and 159 patients from a tertiary cancer referral center who underwent fixation for impending or completed pathologic fractures of long bones were retrospectively analyzed. National Surgical Quality Improvement Program morbidity variables were categorized into medical, surgical, utilization, and all-cause. PFMI, ASA, mCCI, and mFI-5 scores were calculated for each patient. Area under the curve (AUC) was used to compare efficacies. AUCs predicting all-cause morbidity were 0.62, 0.54, and 0.56 for the PFMI, ASA, and mFI-5, respectively. The PFMI outperformed the ASA and mFI-5 in predicting all-cause ( P < 0.01), medical ( P = 0.01), and utilization ( P < 0.01) morbidities. In the 2005 to 2012 subset, the PFMI outperformed the ASA, mFI-5, and mCCI in predicting all-cause ( P = 0.01), medical ( P = 0.03), and surgical ( P = 0.05) morbidities but performed similarly to utilization morbidity ( P = 0.19). In our institutional cohort, the AUC for the PFMI in morbidity stratification was 0.68. The PFMI was associated with all-cause (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.12 to 1.51; P < 0.001), medical (OR, 1.19; 95% CI, 1.03 to 1.40; P = 0.046), and utilization (OR, 1.32; 95% CI, 1.14 to 1.52; P < 0.001) morbidities but not significantly associated with surgical morbidity (OR, 1.21; 95% CI, 0.98 to 1.49; P = 0.08) in this cohort. The PFMI is an advancement in postoperative morbidity risk stratification of patients with pathologic fracture from metastatic disease. III.