Background There is a major drive within healthcare to reduce patient readmissions, from patient care and cost perspectives. Pharmacist-led innovations have been demonstrated to enhance patient outcomes. Objective To assess the impact of a post-discharge, pharmacist-led medicines optimisation clinic on readmission parameters. Assessment of the economic, clinical and humanistic outcomes were considered. Setting Respiratory and cardiology wards in a district general hospital in Northern Ireland. Method Randomised, controlled trial. Blinded random sequence generation; a closed envelope-based system, with block randomisation. Adult patients with acute unplanned admission to medical wards subject to inclusion criteria were invited to attend clinic. Analysis was carried out for intention-to-treat and per-protocol perspectives. Main Outcome Measure 30-day readmission rate. Results Readmission rate reduction at 30 days was 9.6% (P = 0.42) and the reduction in multiple readmissions over 180-days was 29.1% (P = 0.003) for the intention-to-treat group (n = 31) compared to the control group (n = 31). Incidence rate ratio for control patients for emergency department visits was 1.65 (95% CI 1.05-2.57, P = 0.029) compared with the intention-to-treat group. For unplanned GP consultations the equivalent incident rate ratio was 2.00 (95% CI 1.18-3.58, P = 0.02). Benefit to cost ratio in the intention-to-treat and per-protocol groups was 20.72 and 21.85 respectively. Patient Health Related Quality of Life was significantly higher at 30-day (P < 0.001), 90-day (P < 0.001) and 180-day (P = 0.036) time points. A positive impact was also demonstrated in relation to patient beliefs about their medicines and medication adherence. Conclusion A pharmacist-led post-discharge medicines optimisation clinic was beneficial from a patient care and cost perspective.