Introduction: Electronic prescribing systems can improve the quality and safety of healthcare services, but their implementation is not straightforward and may create unexpected change. However, the added complexity of paediatric prescribing (eg, dose calculations, dilutions, manipulations) may pose additional challenges. This study will aim to (1) understand the complex organisational reality of a paediatric hospital in which a new electronic paediatric prescribing (ePP) system will be introduced; (2) describe ePP-related change, over time, in paediatric hospital ward settings; (3) explore staff perspectives in relation to currently established practices and processes; and (4) assess the impact of ePP on care provision and hospital work from the perspective of paediatricians, paediatric nurses and managers. Methods and analysis: A qualitatively driven mixedmethod approach will be adopted, including 3 interrelated substudies. The core component of the study will be qualitative (substudy 1): we will use ethnographic research methods, including nonparticipant observation in wards and informal conversational interviews with members of staff. In addition, the design will include 2 embedded supplementary components: a qualitative 1 (substudy 2) based on in-depth interviews and/or focus groups with paediatricians, paediatric nurses, paediatric pharmacists/pharmacy technicians and managers; and a quantitative 1 (substudy 3) in which a staff survey will be developed and administered before and after the ePP implementation. Analytic themes will be identified from ethnographic field notes and interview data. Survey data will be analysed using descriptive statistics and baseline and follow-up data compared to establish impact evaluation measures. Ethics and dissemination: A favourable ethical opinion has been obtained from a National Health Service (NHS) Research Ethics Committee (15/SS/0157). NHS research governance approval has been obtained at the relevant hospital site. The results of the study will be disseminated through conferences and peer-reviewed journals, as well as fed back to those involved in clinical practice and policy development at the study site.