Little is known about the influence of pre-transplant comorbidities on post-transplant expenditures. We estimated the associations between pre-transplant comorbidities and post-transplant Medicare costs, using several comorbidity classification systems. We included recipients of first-kidney deceased donor transplants from 1995 through 2002 for whom Medicare was the primary payer for at least one year pre-transplant (N = 25,175). We examined pre-transplant comorbidities as classified by International Classification of Diseases (ICD-9-CM) codes from Medicare claims with the Clinical Classifications Software (CCS) and Charlson and Elixhauser algorithms. Post-transplant costs were calculated from payments on Medicare claims. We developed models considering Organ Procurement and Transplantation Network (OPTN) variables plus: 1) CCS categories, 2) Charlson, 3) Elixhauser, 4) number of Charlson and 5) number of Elixhauser comorbidities, independently. We applied a novel regression methodology to account for censoring. Costs were estimated at individual and population levels. The comorbidities with the largest impact on mean Medicare payments included cardiovascular disease, malignancies, cerebrovascular disease, mental conditions and functional limitations. Skin ulcers and infections, rheumatic and other connective tissue disease and liver disease also contributed to payments and have not been considered or described previously. A positive graded relationship was found between costs and the number of pre-transplant comorbidities. In conclusion, we showed that expansion beyond the usually considered pre-transplant comorbidities with inclusion of CCS and Charlson or Elixhauser comorbidities increased the knowledge about comorbidities related to augmented Medicare payments. Our expanded methodology can be used by others to assess more accurately the financial implications of renal transplantation to Medicare and individual transplant centers.