Background: Medicine prescribing, monitoring and administration in care homes can be significantly enhanced. Effective interventions to improve pharmaceutical care and resident outcomes are required. The enablement of pharmacists to prescribe provides an opportunity for pharmacist independent prescribers to assume responsibility for improving pharmaceutical care, medication-related outcomes and resident safety whilst reducing general practitioner workload. Objective(s): To determine the effectiveness and cost-effectiveness of pharmacist independent prescribing in care homes. Design: Development work was undertaken through five work packages before the delivery of the definitive trial. Triads of pharmacist independent prescribers, care home and general practice with responsibility over 20 care home residents were recruited and cluster randomised to intervention or usual care for 6 months. Researchers were blinded at recruitment stage only. Recruitment of 880 residents was required to provide 80% statistical power, to show a 21% reduction in falls over 6 months, assuming 20% attrition. Randomisation was undertaken electronically at triad level, stratified by geographical area. Intention-to-treat analysis undertaken using a negative binomial model. Parameters were estimated using a generalised estimating equation approach. Costs were captured from an NHS perspective. Quality of life (EuroQol; five domain; five level) was collected by proxy to enable cost/ quality-adjusted life-year estimation. A concurrent process evaluation was performed. Safety was monitored through a review of pharmacist independent prescriber activities, independent concerns reporting and review of adverse events. Participants: Forty-nine triads of general practitioners, pharmacist independent prescribers and care homes were recruited with 454 residents allocated to the intervention arm and 428 to the control arm. Intervention: Medication review and care planning, medication reconciliation, staff training, support with care home medication-related procedures, deprescribing and authorisation of monthly prescriptions. Main outcome measure: Fall rate per person over ó months. Results: Data for 449 intervention and 427 control residents available for final analysis.