OBJECTIVES: In 2008, Medicare established nonpayment policy for HAPU incidences, prompting hospitals to adopt quality improvement (QI) interventions that could support implementation of evidence-based practices (EBPs) for HAPU prevention. The objective of this study is to evaluate the longitudinal impact of CMS policy and EBP implementation on HAPU incidence. METHODS: We characterized longitudinal adoption of 25 QI interventions to implement EBPs. Counts of quarterly HAPU incidence were collected at the hospital-level from 55 University HealthSystem Consortium (UHC) hospitals between 2007-2012. We also monitored time points when QI interventions resulted in direct improvements to implementation of EBPs. Two-level mixed effects Poisson regression with empirical Bayes estimates models were developed to test the longitudinal association between CMS policy, EBPs and HAPU incidence by hospital-quarter. First, a model tested the effects of 25 categorical QI interventions bundled with EBPs as indicated by hospitals. Second, a model tested the effect of hospital-wide implementation of EBPs on HAPU incidence, controlling for EBP-time interaction. Each model included fixed effects for QI interventions, CMS policy, age, and case-mix index. The models assumed level-2 random effects for intercepts, CMS policy and EBP implementation. Both models included an offset to control for variability in number of inpatient hospitalizations.  RESULTS: First, controlling for 25 categorical QI interventions, the EBPs for HAPU prevention had a significant effect on HAPU incidence (-0.1808 HAPU cases per quarter; p=0.0325). CMS policy had the largest significant effect on HAPU incidence (-1.13 cases per quarter; p<0.001). Second, direct effect of EBPs on HAPU incidence, not controlling for QI interventions, was greater (-0.27 cases per quarter; p=0.002). The effect of time on HAPU incidence was significant in both models, approximately -0.03 cases per quarter. CONCLUSIONS: HAPU prevention is closely associated with increased adoption of QI interventions and improved implementation of EBPs for HAPU prevention.