Abstract Aims Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI). Methods and results Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70–0.84); all-cause mortality 0.71 (0.63–0.80); CV mortality 0.68 (0.57–0.81); MI 0.81 (0.73–0.91); ischaemic stroke 0.76 (0.62–0.93); heart failure hospitalization 0.73 (0.63–0.85), and coronary artery revascularization 0.86 (0.79–0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin. Conclusions Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit.