Background: Most patients are recommended secondary prevention pharmacotherapies following an acute coronary syndromes (ACS). Aim: To identify predictors of adherence at 6 months and strategies to improve adherence to these therapies. Methods: Patients in the CONCORDANCE registry who were discharged on evidence-based medications were stratified into those receiving ≥75% (‘adherent’) or <75% (‘non-adherent’) of indicated medications at 6 months. Baseline characteristics, hospital and post-discharge care were compared between groups. Multivariable logistic analysis identified independent predictors of adherence. The relative contribution of each clinical or treatment factor to ‘adherence’ was determined using an adequacy measure method. Results: Follow-up data were available for 6595 patients, 4492 (68.1%) of whom were ‘adherent’. Clinical factors predictive of adherence included previous stroke, percutaneous coronary intervention (PCI) and hypertension (odds ratios (OR) 1.36–1.56); factors predictive of non-adherence included discharge diagnosis of non–ST-segment elevation myocardial infarction (vs unstable angina) (OR 0.51) and atrial fibrillation (OR 0.59). Discharge on ≥75% of indicated medications was a strong predictor of adherence at 6 months (OR 10.23, 95% confidence interval 7.89−13.27); in-hospital management factors predicting non-adherence were medical management alone (OR 0.34) and coronary artery bypass graft (OR 0.50) (both vs PCI). Post-discharge predictors of adherence included cardiac rehabilitation (OR 1.36) and general practitioner attendance (OR 1.40). Conclusion: Failure to discharge patients on indicated therapies is the most important modifiable predictor of adherence failure 6 months after an ACS. Implementing protocols to automate prescription of indicated discharge therapies, has the potential to reduce non-adherence dramatically in the 6 months following discharge.