Building high reliable healthcare systems to reduce avoidable patient harm is a global priority. However, there is variability in the application and understanding of the previously identified High Reliability Organization (HRO) principles to make improvements. We describe specific organizational activities exemplifying the five HRO principles during the planning and go-live periods of the new Electronic Health Record (EHR) system at a multi-site academic health sciences centre in Ontario, Canada. Further, we describe a case example where all five HRO principles were exemplified during EHR implementation. Overall, 23 activities exemplifying organizational anticipation and resiliency were identified. Of the 23 activities, 12 occurred during the preparing for go-live and 11 activities occurred during the go-live periods. This paper demonstrates how HRO principles can be used in healthcare to detect and adapt to patient safety threats, in order to prevent avoidable patient harm during large scale change.