Objectives: To conduct a systematic review and narrative synthesis of interventions based on secondary use of data (SUD) from electronic prescribing (EP) and electronic hospital pharmacy (EHP) systems and their effectiveness in secondary care, and to identify factors influencing SUD. Method: The search strategy had four facets: 1. Electronic databases, 2. Medication safety, 3. Hospitals and quality/safety, and 4. SUD. Searches were conducted within EMBASE, Medline, CINAHL, and International Pharmaceutical Abstracts. Empirical SUD intervention studies that aimed to improve medication safety and/or quality, and any studies providing insight into factors affecting SUD were included. Results: We identified nine quantitative studies of SUD interventions and five qualitative studies. SUD interventions were complex and fell into four categories, with ‘provision of feedback’ the most common. While heterogeneous, the majority of quantitative studies reported positive findings in improving medication safety but little detail was provided on the interventions implemented. The five qualitative studies collectively provide an overview of the SUD process, which typically comprised nine steps from data identification to analysis. Factors influencing the SUD process were electronic systems implementation and level of functionality, knowledge and skills of SUD users, organisational context, and policies around data reuse and security. Discussion and Conclusion: The majority of the SUD interventions were successful in improving medication safety, however, what contributes to this success needs further exploration. From synthesis of research evidence in this review, an integrative framework was developed to describe the processes, mechanisms, and barriers for effective SUD.