INTRODUCTION: Multimorbidity in surgery is common and associated with worse postoperative outcomes. However, the conventional multimorbidity definition (two or more comorbidities) labels the vast majority of elderly patients as multimorbid, limiting its clinical benefit. We developed and validated a better surgical specialty-specific multimorbidity definition based on distinct comorbidity combinations called qualifying comorbidity sets (QCSs). METHODS: We used Medicare claims data for patients aged 66 to 90 years hospitalized for general (GS), orthopedic (OS), or vascular surgery (VS). Using 2016 to 2017 data, we identified all comorbidity combinations associated with a double-or-greater risk of 30-day mortality compared with the overall population undergoing the same procedure; these were defined as QCSs. We applied these QCSs to 2018 to 2019 data (GS = 462,904 patients, OS = 1,493,999, VS = 301,336) to obtain 30-day mortality estimates. For further validation, we tested whether multimorbid patients treated at better-resourced (based on nursing resources, surgical volume, teaching status) vs other hospitals had differential outcomes using multivariate matching. RESULTS: Compared with the conventional multimorbidity definition, the QCS-based definition labeled fewer patients as multimorbid: GS = 85.0% vs 55.9% (p < 0.0001); OS = 66.6% vs 40.2% (p < 0.0001); VS = 96.2% vs 52.7% (p < 0.0001) (Table). Thirty-day mortality was higher by the QCS-based definition: GS = 3.96% (conventional) vs 5.64% (QCS-based) (p < 0.0001); OS = 1.13% vs 1.68% (p < 0.0001); VS = 4.43% vs 7.00% (p < 0.0001). Better-resourced hospitals offered larger mortality benefit for multimorbid vs nonmultimorbid GS and OS patients (GS absolute risk reduction difference-in-difference = −0.94% [95% CI −1.24%, −0.63%], p < 0.0001; OS difference-in-difference = −0.20% [95% CI −0.29%, −0.10%], p < 0.0001). CONCLUSION: Our QCS-based multimorbidity definition identifies a more specific, higher risk pool of patients compared with the conventional definition, allowing for better clinical decision-making. Table. - Rate of Multimorbidity and 30-Day Mortality with Conventional vs New Qualifying Comorbidity Set-Based Definitions Variable General surgery General surgery Orthopedic surgery Orthopaedic surgery Categorizations Frequency (% (N)) Mortality rate Frequency (% (N)) Mortality rate All patients 100.00% (230,410) 3.42% 100.00% (778,131) 0.79% Conventional multimorbidity definition Nonmultimorbid (0-1 comorbidities) 14.98% (34,521) 0.37% 33.36% (259,570) 0.12% Multimorbid (≥2 comorbidities) 85.02% (195,889) 3.96% 66.64% (518,561) 1.13% New multimorbidity definition Nonmultimorbid (QCS = 0) 44.11% (101,624) 0.61% 59.85% (465,702) 0.20% Multimorbid (QCS ≥ 1) 55.89% (128,786) 5.64% 40.15% (312,429) 1.68%