The Centers for Medicare and Medicaid Services (CMS) decision to withhold payment for certain hospital-acquired conditions has prompted widespread efforts to prevent such events, including health care–associated infections. Prior research suggests that academic centers and safety-net hospitals may be disproportionately affected by financial penalties imposed by CMS through various pay-for-performance initiatives. In this study, investigators analyzed how hospital size affected performance in the Hospital-Acquired Condition Reduction Program. They concluded that hospital size leads to bias when evaluating hospital performance, disproportionately penalizing larger hospitals when the expected complication rate for a particular event is low. The authors provide numerous suggestions for improving the evaluation of hospital performance within the program.