The quality of care for Swedish patients with acute myocardial infarction (AMI) is continuously increasing. Nevertheless, a great potential for improvement still exists. The aim of the present study was to design and implement a systematic quality improvement (QI) collaborative in the area of AMI care, and to validate its usefulness primarily by analyzing its effect on hospital adherence to national guidelines. Also, the impact on patient morbidity and mortality was to be evaluated. The intervention was based on proven QI methodologies, as well as interactive use of a web-based quality registry with enhanced, powerful feedback functions. 19 hospitals in the intervention group were matched to 19 similar control hospitals. In comparison with the control group, the intervention group showed significantly higher post-interventional improvements in 4 out of 5 analyzed quality indicators (significance shown for ACE-inhibitors, Clopidogrel, Heparin/LMWH, Coronary angiography, no significance for Lipid-lowering therapy). From baseline to the post-intervention measurement, the intervention hospitals showed significantly lower all-cause mortality and cardiovascular re-admission rates (events per 100 patient-years; -2,82, 95% CI -5,26 to -0,39; -9,31, 95% CI -15,48 to -3,14, respectively). No significant improvements were seen in the control group. The improved guideline adherence rates in the intervention hospitals were sustained for all indicators but one (ACE-inhibitors), this during a follow-up measurement three months after study support withdrawal. No effects were seen on any indicators other than those primarily targeted. In conclusion, by combining a systematic QI collaborative with the utilization of a national quality registry, significant improvements in quality of care for patients with AMI can be achieved.