Implementation of an electronic medical record (EMR) is a significant workplace event for nurses in hospitals. Understanding nurses’ key concerns can inform EMR implementation and ongoing optimisation strategies to increase the likelihood of nurses remaining in the nursing workforce. This concurrent mixed-methods study included surveys from 540 nurses (response rate 15.5%), and interviews with 63 nurses to examine their perceptions of using a new EMR prior to implementation at a single healthcare organisation. Survey findings revealed 32.2% (n = 174) of nurses reported low well-being scores and 28.7% (n = 155) were experiencing burnout symptoms. In contrast, 40.3% (n = 216) of nurses reported high work satisfaction, 62.3% (n = 334) had high intentions of staying in their role, and 34.3% (n = 185) were engaged in their work. Nearly half (n = 250, 46.3%) reported intrinsic motivation towards EMR use. Thematic analysis of focus group interviews revealed two themes, each with three subthemes: (1) Us and Them, detailed the juxtaposition between nurses’ professional role and anticipated changes imposed on them and their work with the EMR implementation; and (2) Stuck in the middle, revealed nurses’ expectations and anticipations about how the EMR may affect the quality of nurse-patient relationships. In conclusion, anticipation of the EMR implementation emerged as a stressor for nursing staff, with some groups of nurses particularly vulnerable to negative consequences to their well-being.