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Background. The Veterans Health Administration (VHA) introduced the Methicillin-Resistant Staphylococcus aureus (MRSA) Prevention Initiative in March 2007. Although the initiative has been perceived as a vertical intervention focusing on MRSA, it also expanded infection prevention and control programs and resources. We aimed to assess the horizontal effect of the initiative on hospital-onset (HO) gram-negative rod (GNR) bacteremia.Methods. This retrospective cohort included all patients who had HO bacteremia due to Escherichia coli, Klebsiella species, or Pseudomonas aeruginosa at 130 VHA facilities from January 2003 to December 2013. The effects were assessed using segmented linear regression with autoregressive error models, incorporating autocorrelation, immediate effect, and time before and after the initiative. Community-acquired (CA) bacteremia with same species was also analyzed as nonequivalent dependent controls.Results. A total of 11 196 patients experienced HO-GNR bacteremia during the study period. There was a significant change of slope in HO-GNR bacteremia incidence rates from before the initiative (+0.3%/month) to after (–0.4%/month) (P < .01), while CA GNR incidence rates did not significantly change (P = .08). Cumulative effect of the intervention on HO-GNR bacteremia incidence rates at the end of the study period was estimated to be −43.2% (95% confidence interval, −51.6% to −32.4%). Similar effects were observed in subgroup analyses of each species and antimicrobial susceptibility profile.Conclusions. Within 130 VHA facilities, there was a sustained decline in HO-GNR bacteremia incidence rates after the implementation of the MRSA Prevention Initiative. As these organisms were not specifically targeted, it is likely that horizontal components of the initiative contributed to this decline.