ObjectiveTo examine the effectiveness and cost-effectiveness of the community pharmacy New Medicine Service (NMS) at 26 weeks.MethodsPragmatic patient-level parallel randomised controlled trial in 46 English community pharmacies. 504 participants aged ≥14, identified in the pharmacy when presenting a prescription for a new medicine for predefined long-term conditions, randomised to receive NMS (n=251) or normal practice (n=253) (NMS intervention: 2 consultations 1 and 2 weeks after prescription presentation). Adherence assessed through patient self-report at 26-week follow-up. Intention-to-treat analysis employed. National Health Service (NHS) costs calculated. Disease-specific Markov models estimating impact of non-adherence combined with clinical trial data to calculate costs per extra quality-adjusted life-year (QALY; NHS England perspective).ResultsUnadjusted analysis: of 327 patients still taking the initial medicine, 97/170 (57.1%) and 103/157 (65.6%) (p=0.113) patients were adherent in normal practice and NMS arms, respectively. Adjusted intention-to-treat analysis: adherence OR 1.50 (95% CI 0.93 to 2.44, p=0.095), in favour of NMS. There was a non-significant reduction in 26-week NHS costs for NMS: −£104 (95% CI −£37 to £257, p=0.168) per patient. NMS generated a mean of 0.04 (95% CI −0.01 to 0.13) more QALYs per patient, with mean reduction in lifetime cost of −£113.9 (−1159.4, 683.7). The incremental cost-effectiveness ratio was −£2758/QALY (2.5% and 97.5%: −38 739.5, 34 024.2. NMS has an 89% probability of cost-effectiveness at a willingness to pay of £20 000 per QALY.ConclusionsAt 26-week follow-up, NMS was unable to demonstrate a statistically significant increase in adherence or reduction in NHS costs, which may be attributable to patient attrition from the study. Long-term economic evaluation suggested NMS may deliver better patient outcomes and reduced overall healthcare costs than normal practice, but uncertainty around this finding is high.Trial registration numberNCT01635361, ISRCTN23560818, ISRCTN23560818, UKCRN12494.