Aggressively managing low-density lipoprotein cholesterol (LDL-C) after myocardial infarction (MI) is a cornerstone of secondary prevention. The changes in LDL-C after MI and the factors associated with LDL-C levels are unknown. Therefore, we directly measured fasting LDL-C levels in 797 MI patients from 24 US hospitals from 2005 to 2008. Mean LDL-C levels at discharge, 1 month, and 6 months were 95.1, 81.9, and 87.1 mg/dL, respectively. In a hierarchical, multivariable, repeated measures model, older age, male sex, and hypertension were associated with lower LDL-C levels, whereas self-reported avoidance of health care because of cost was associated with higher LDL-C. Both the presence and intensity of statin therapy at discharge were strongly associated with LDL-C levels, with adjusted mean 6-month changes of −3.4 mg/dL (95% confidence interval (CI): −12.1, 5.3) for no statins; 1.7 mg/dL (95% CI: −4.7, 8.1) for low statins; −10.2 mg/dL (95% CI: −14.5, −6.0) for moderate statins; and −13.9 mg/dL (95% CI: −19.7, −8.0) for intensive statins (P < 0.001). In conclusion, we found that greater reductions in LDL-C levels after MI were strongly associated with the presence and intensity of statin therapy, older age, male sex, hypertension, and better socioeconomic status. These findings support the use of intensive statin therapy in post-MI patients and provide estimates of the expected LDL-C changes after MI in a real-world population.