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<p><strong>Background</strong> The electronic medical records software of the Catalan Institute of Health has recently incorporated an electronic version of clinical practice guidelines (e-CPGs). This study aims to assess the impact of the implementation of e-CPGs on the diagnosis, treatment, control and management of hypercholesterolaemia, diabetes mellitus type 2 and hypertension.</p><p><strong>Methods</strong> Eligible study participants are those aged 35–74 years assigned to family practitioners (FPs) of the Catalan Institute of Health. Routinely collected data from electronic primary care registries covering 80% of the Catalan population will be analysed using two approaches: (1) a cross-sectional study to describe the characteristics of the sample before e-CPG implementation; (2) a controlled before-and-after study with 1-year follow-up to ascertain the effect of e-CPG implementation. Patients of FPs who regularly use the e-CPGs will constitute the intervention group; the control group will comprise patients assigned to FPs not regularly using the e-CPG. The outcomes are: (1) suspected and confirmed diagnoses, (2) control of clinical variables, (3) requests for tests and (4) proportions of patients with adequate drug prescriptions.</p><p><strong>Results</strong> This protocol should represent a reproducible process to assess the impact of the implementation of e-CPGs. We anticipate reporting results in late 2013.</p><p><strong>Conclusion</strong> This project will assess the effectiveness of e-CPGs to improve clinical decisions and healthcare procedures in the three disorders analysed. The results will shed light on the use of evidence-based medicine to improve clinical practice of FPs.</p>