BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) mandate that orthotopic heart transplantation (OHT) centers perform 10 transplants per year to qualify for funding. We sought to determine whether this cutoff is meaningful and establish recommendations for optimal center volume using the United Network for Organ Sharing (UNOS) registry. METHODS: We reviewed UNOS data (years 1999 to 2006) identifying 14,401 first-time adult OHTs conducted at 143 centers. Stratification was by mean annual institution volume. Primary outcomes of 30-day and 1-year mortality were assessed by multivariable logistic regression (adjusted for comorbidities and risk factors for death). Sequential volume cutoffs were examined to determine if current CMS standards are optimal. Pseudo R2 and area under the receiver operating curve assessed goodness of fit. RESULTS: Mean annual volume ranged from 1 to 90. One-year mortality was 12.6% (n = 1,800). Increased center volume was associated with decreased 30-day mortality (p < 0.001). Decreased center volume was associated with increases in 30-day (odds ratio [OR] 1.03, 95% confidence interval [CI]: 1.02 to 1.03, p < 0.001) and 1-year mortality (OR 1.01, 95% CI: 1.01 to 1.02, p = 0.03--censored for 30-day death). The greatest mortality risk occurred at very low volume centers (