OBJECTIVE: To examine race and gender cost differences associated with treating atrial fibrillation (AF) in the inpatient setting. METHODS: This retrospective study analyzed nationally representative hospital discharge data from the 2001 Health Care Cost and Utilization Project (HCUP) database. The impact of race and gender on costs of treating AF as a primary diagnosis (ICD-9 427.31) and as a comorbid diagnosis was examined. Using the five most frequent principal discharge diagnoses (CAD, CHF, pneumonia, COPD, MI) with AF as a comorbid diagnosis (case), a case/control analysis was performed to estimate annual incremental costs of AF. Cases were matched to controls on age, gender, race, principal discharge diagnosis, and hospital bed size. Ordinary least squares regression was used with the following covariates: age, gender, race, payer, bed size, emergency admission, unrelated surgery, and comorbidities. RESULTS: There were 348,000 hospitalizations for AF as principal diagnosis with a cost of $2.56 billion. Among the top five HCUP diagnoses with AF as a comorbid diagnosis, there were 547,000 hospitalizations with an incremental cost of $1.5 billion. Although race and gender did not significantly affect the costs of hospitalizations for AF as a principal diagnosis, non-white race was associated with significantly (P<0.001) higher costs among the top five HCUP diagnoses with AF as a comorbid diagnosis with costs ranging from $1216 (CHF) to $2537 (MI) per hospitalization. Female gender was associated with significantly increased costs for pneumonia and COPD, but decreased costs for CHF and MI. CONCLUSIONS: Neither gender nor race affect costs when treating AF as a principal diagnosis. Non-white race is associated with higher costs in treating top five HCUP diagnoses with comorbid AF.