Abstract Introduction Hypercholesterolemia is a well-known risk factor for developing atherosclerosis and subsequently for the risk of a myocardial infarction (MI). Moreover, it might also be related to the extent of damaged myocardium in the event of a MI. The aim of this study was to evaluate the association of baseline low density lipoprotein-cholesterol (LDL-c) level with infarct size in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneously coronary intervention (pPCI). Methods Baseline blood samples were obtained from all patients admitted between 2004 and 2014 with STEMI who underwent pPCI. Patients were excluded in case of out of hospital cardiac arrest, treatment delay of at least 10 h or no complete reperfusion after pPCI in the culprit vessel. Peak creatine kinase (CK) level was used for infarct size estimation, defined as the maximal value during admission. Results A total of 2248 patients were included in this study (mean age 61.8 ± 12.2 years; 25.0% female). Mean LDL-c level was 3.6 ± 1.1 mmol/L and median peak CK level was 1275 U/L (IQR 564–2590 U/L). Baseline LDL-c level [β = 0.041; (95% CI 0.019–0.062); p < 0.001] was independently associated with peak CK level. Furthermore, left anterior descending artery as culprit vessel, initial TIMI 0–1 flow in the culprit vessel, male gender, and treatment delay were also correlated with high peak CK level (p < 0.05). Prior aspirin therapy was associated with lower peak CK level [β = − 0.073 (95% CI − 0.146 to 0.000), p = 0.050]. Conclusion This study demonstrates that besides the more established predictors of infarct size, elevated LDL-c is associated with augmented infarct size in patients with STEMI treated with pPCI.