Background Medication errors are common in primary care and are associated with considerable risk of patient harm. We tested whether a pharmacist-led, information technology-based intervention was more eff ective than simple feedback in reducing the number of patients at risk of measures related to hazardous prescribing and inadequate blood-test monitoring of medicines 6 months after the intervention. Methods In this pragmatic, cluster randomised trial general practices in the UK were stratifi ed by research site and list size, and randomly assigned by a web-based random isation service in block sizes of two or four to one of two groups. The practices were allocated to either computer-generated simple feedback for at-risk patients (control) or a pharmacist-led information technology intervention (PINCER), composed of feedback, educational outreach, and dedicated support. The allocation was masked to general practices, patients, pharmacists, researchers, and statisticians. Primary outcomes were the proportions of patients at 6 months after the intervention who had had any of three clinically important errors: non-selective non-steroidal anti-infl ammatory drugs (NSAIDs) prescribed to those with a history of peptic ulcer without co-prescription of a proton-pump inhibitor; β blockers prescribed to those with a history of asthma; long-term prescription of angiotensin converting enzyme (ACE) inhibitor or loop diuretics to those 75 years or older without assessment of urea and electrolytes in the preceding 15 months. The cost per error avoided was estimated by incremental cost-eff ectiveness analysis. This study is registered with Controlled-Trials. com, number ISRCTN21785299. Findings 72 general practices with a combined list size of 480 942 patients were randomised. At 6 months' follow-up, patients in the PINCER group were signifi cantly less likely to have been prescribed a non-selective NSAID if they had a history of peptic ulcer without gastroprotection (OR 0.58, 95% CI 0.38-0.89); a β blocker if they had asthma (0.73, 0.58-0.91); or an ACE inhibitor or loop diuretic without appropriate monitoring (0.51, 0.34-0.78). PINCER has a 95% probability of being cost eff ective if the decision-maker's ceiling willingness to pay reaches £75 per error avoided at 6 months. Interpretation The PINCER intervention is an eff ective method for reducing a range of medication errors in general practices with computerised clinical records. Funding Patient Safety Research Portfolio, Department of Health, England.