BACKGROUND: The purpose of this research is to develop and evaluate methods for conducting pragmatic cluster randomized trials in a primary care electronic database. The proposal describes one application, in a less frequent chronic condition of public health importance, secondary prevention of stroke. A related protocol in antibiotic prescribing was reported previously. METHODS/DESIGN: The study aims to implement a cluster randomized trial (CRT) using the electronic patient records of the General Practice Research Database (GPRD) as a sampling frame and data source. The specific objective of the trial is to evaluate the effectiveness of a computer-delivered intervention at enhancing the delivery of stroke secondary prevention in primary care. GPRD family practices will be allocated to the intervention or usual care. The intervention promotes the use of electronic prompts to support adherence with the recommendations of the UK Intercollegiate Stroke Working Party and NICE guidelines for the secondary prevention of stroke in primary care. Primary outcome measure will be the difference in systolic blood pressure between intervention and control trial arms at 12-month follow-up. Secondary outcomes will be differences in serum cholesterol, prescribing of antihypertensive drugs, statins, and antiplatelet therapy. The intervention will continue for 12 months. Information on the utilization of the decision-support tools will also be analyzed. DISCUSSION: The CRT will investigate the effectiveness of using a computer-delivered intervention to reduce the risk of stroke recurrence following a first stroke event. The study will provide methodological guidance on the implementation of CRTs in electronic databases in primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN35701810.