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To establish the effectiveness of clinical guideline implementation strategies.Systematic reviews in full text, English language, 1987–2007, reporting any measure of clinical process change or cost–benefit analysis.Overview of secondary evidenceIndependent critical appraisal using AMSTAR, primary author undertaking all data extraction using a purpose-built form.We identified 144 potential papers, from which 33 systematic reviews were included. These reflected 714 primary studies involving 22 512 clinicians, in a range of health care settings. Implementation strategies were varied, rarely comparable, with variable outcomes. Effective implementation strategies included multifaceted interventions, interactive education and clinical reminder systems. Didactic education and passive dissemination strategies were ineffective. Cost-effectiveness studies were rare.Successful guideline implementation strategies should be multifaceted, and actively engage clinicians throughout the process.