The effects of electronic health record (EHR) implementation on safety culture are unclear. EHR adoption is disruptive to clinician workflow, affecting work satisfaction and increasing physician and nurse burnout. This could plausibly manifest as worsened safety culture after EHR implementation. In this study, which used AHRQ Hospital Survey on Patient Safety Culture data at 190 hospitals between 2007 and 2011, EHR adoption was associated with mixed effects on safety culture. No overall relationship was found between EHR implementation and safety culture. In fact, fewer patient safety events were reported following EHR adoption, which may reflect safer care or conversely could represent challenges with reporting events in the electronic systems. Early adopters of EHRs did appear to have a stronger culture of safety, but this finding could either mean that EHRs improved safety or that hospitals that emphasized other measures to improve safety culture also tended to adopt EHRs earlier. As this study illustrates, the profound workflow shifts associated with EHR implementation likely induce complex effects that could improve or impair safety. A previous PSNet interview described the role of health information technology in patient safety.