We studied approaches to comorbidity risk adjustment by comparing two ICD-9-CM adaptations (Deyo, Dartmouth-Manitoba) of the Charlson comorbidity index applied to Massachusetts coronary artery bypass surgery data. We also developed a new comorbidity index by assigning study-specific weights to the original Charlson comorbidity variables. The 2 ICD-9-CM coding adaptations assigned identical Charlson comorbidity scores to 90% of cases, and specific comorbidities were largely found in the same cases (kappa values of 0.72-1.0 for 15 of 16 comorbidities). Meanwhile, the study-specific comorbidity index identified a 10% subset of patients with 15% mortality, whereas the 5% highest-risk patients according to the Charlson index had only 8% mortality (p = 0.01). A model using the new index to predict mortality had better validated performance than a model based on the original Charlson index (c = 0.74 vs. 0.70). Thus, in our population, the ICD-9-CM adaptation used to create the Charlson score mattered little, but using study-specific weights with the Charlson variables substantially improved the power of these data to predict mortality.