Background: The SPPiRE cluster randomised controlled trial (RCT) found that a GP delivered medication review that incorporated screening potentially inappropriate prescriptions (PIP), a brown bag review and a patient priority assessment, resulted in a significant but small reduction in the number of medicines and no significant reduction in PIP. Objective: To explore the experiences of GPs and patients engaged in the SPPiRE intervention and the potential for system wide implementation.Design: Mixed methods process evaluation; quantitative data was collected from the SPPiRE intervention website and qualitative data via semi-structured interviews.Setting and participants: 51 general practices throughout Ireland, and 404 participants with multimorbidity aged ≥65 years, prescribed ≥15 medicines participated in the RCT. Qualitative data was collected with purposive samples of intervention GPs (18/26) and patients (27/208). Methods: Quantitative data was analysed descriptively, qualitative data thematically and both were integrated using a triangulation protocol.Results: The analysis generated three themes, intervention implementation, mechanisms of action, and both were underpinned by the theme of context. One fifth of patients had no review, primarily due to insufficient GP time. The brown bag review component resulted in the most medication changes, particularly stopping a medicine. GPs felt it easier to change medicines if the patient was well known to them, and patients were generally receptive to change. GPs identified lack of integration into practice software systems and resources as barriers to future implementation.Conclusion: Consideration of implementation of successful interventions is key to informing policy and integration into clinical practice. GPs and patients viewed the intervention positively, but implementation will depend on resourcing and integration into practice software systems.Trial registration number: ISRCTN12752680