With increased scrutiny regarding the cost and safety of health care delivery, there is increasing interest in judicious patient selection for total joint arthroplasty (TJA) procedures. It is unknown which comorbidities incur the greatest increase in risk to the patient and cost to the system after TJA. Therefore, this study sought to characterize the association of common preoperative comorbidities with both the risk for postoperative in-hospital complications and the total hospital cost in patients undergoing TJA.A retrospective cohort study was conducted using the National Inpatient Sample. All elective, unilateral, primary or revision total knee or hip arthroplasty procedures in patients aged 40-95 years from 2008 to 2012 were identified. Common preoperative comorbidities were identified with use of clinical comorbidity software. Risk of complication and cost were calculated for each comorbidity.A total of 4,323,045 patients were identified. Patient comorbidities increased the risk of major postoperative complications, with the highest risk associated with congestive heart failure (CHF; relative risk [RR], 4.402), valvular heart disease (VHD; RR, 3.209), and chronic obstructive pulmonary disease (COPD; RR, 2.813). Likewise, comorbidities increased overall hospital costs, with the largest additional costs associated with coagulopathy (+$3787), CHF (+$3701), and electrolyte disorders (+$3179). The cumulative number of comorbidities was associated with increased risk (R2 = 0.86) and cost (R2 = 0.90).The findings of our study suggest that greater comorbidity burden is associated with increased risk and cost in TJA. Specifically, this article identifies the patient comorbidities that incur the greatest increase in postoperative complications (CHF, VHD, COPD) and cost (coagulopathy, CHF, electrolyte disorders) after TJA.