Multiple key cardiology trials with the potential to change practice or advance understanding have been presented over the past 12 months at international meetings, including the American College of Cardiology (ACC, Chicago, USA, March 2012), European Association for Percutaneous Cardiovascular Interventions (EuroPCR, Paris, France, May 2012), European Society of Cardiology (ESC, Munich, Germany, August 2012), Transcatheter Cardiovascular Therapeutics (TCT, Miami, USA, October 2012), and the American Heart Association (AHA, Los Angeles, USA, November 2012). In this paper, the authors describe and place in clinical context new acute coronary syndrome data, including use of oral antiplatelets and anticoagulants (prasugrel, rivaroxaban, vorapaxar), personalized antiplatelet therapy guided by platelet aggregometry, glucose-insulin-potassium infusion, and changing trends in myocardial infarction. New trial data are also described for interventional cardiology (revascularization in multivessel disease, fractional flow reserve-guided intervention, radial access, bioabsorbable polymer stents, drug-eluting balloons, intraaortic balloon pump use, transcatheter aortic valve implantation), in heart failure (copeptin, angiotensin receptor neprilysin inhibition, aldosterone blockade in diastolic heart failure, biventricular pacing), atrial fibrillation (surgical ablation, antithrombotic strategy after stenting), implantable defibrillator use, and in prevention (renal denervation in hypertension, dalcetrapib, lomitapide, proprotein convertase subtilisin/kexin type 9 in dyslipidemia, insulin glargine/fish oils, and bariatric surgery in diabetes).