Background Guideline-recommended pharmacotherapy after myocardial infarction (MI) has been shown to reduce cardiovascular morbidity and mortality. Our objectives were to determine factors of, and to measure outcomes associated with nonadherence after MI. Design Multicentre, prospective, observational study (Acute Coronary Syndromes Registry). Methods We analyzed data of 11 823 consecutive hospital survivors of acute MI and evaluated their discharge medication with the five following drugs: acetyl salicylic acid, clopidogrel, beta-blocker, angiotensin-converting enzyme inhibitor/sartan and statin. Patients receiving less than four drugs (group 1, n = 3439, 29.1%) were compared with those receiving 4-5 drugs (group 2, n = 8384, 70.9%). The impact of clinical, demographic and treatment factors on not prescribing each of these five drugs at discharge was investigated by using multiple logistic regression models. Results Patients of group 1 were older, had more comorbidities, more frequently suffered a nonST elevation MI and less often received reperfusion therapy. In the multivariate analysis, group 1 was associated with an increased risk for death at 1-year follow-up [ odds ratio (OR): 1.6, 95% confidence interval (CI): 1.4-1.9]. After adjustment for confounding variables chronic oral anticoagulation was the strongest predictor for not receiving acetyl salicylic acid (OR: 19.6, 95% CI: 15.9-24.0) at discharge, no percutaneous coronary intervention within 48 h for not receiving statin (OR: 2.1, 95% CI: 1.9-2.4) and clopidogrel (OR: 10.4, 95% CI: 9.4-11.5), chronic obstructive lung disease for not receiving beta-blocker (OR: 4.2, 95% CI: 3.6-4.9) and chronic renal insufficiency for not receiving angiotensin-converting enzyme inhibitor/sartan (OR: 2.8, 95% CI: 2.2-3.5). Conclusion In clinical practice guideline-adherent secondary prevention drug therapy is linked with an improved 1-year survival. Comorbidities and no interventional treatment were strong negative predictors for guideline-adherent discharge medication. Eur J Cardiovasc Prev Rehabil 17:576-581 (C) 2010 The European Society of Cardiology