Background: Patients with acute coronary syndrome (ACS) still have high rates of recurrent adverse cardiovascular events. The purpose of this study was to evaluate the effects of changes in the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases for intensive lipid-lowering therapy on the prescription status, lipid profile and clinical outcomes among Japanese patients with ACS. Methods: Data were retrospectively analysed for 283 consecutive patients with de novo ACS who underwent primary percutaneous coronary intervention and received follow-up coronary angiography between January 2012 and September 2019. Patients were divided into two groups according to the to onset of ACS relative to the guideline update – before (Group 1; n=182) and after (Group 2; n=101). Changes in prescription status, lipid profile and clinical outcomes (composite of cardiac death and non-fatal MI, coronary events from culprit and non-culprit lesions) were evaluated. Results: Post-treatment LDL concentrations were significantly lower in Group 2, but target LDL concentrations of <1.81 mmol/l were only achieved in 58.4% of patients. In Group 2, 85% of patients who received combination high-intensity statin/ezetimibe therapy achieved the target LDL. After propensity score matching, the incidence of coronary events from non-culprit lesions was significantly lower in Group 2 than Group 1 (3.0% versus 19.4%, respectively; p<0.01). Cox model analysis showed that the guideline update resulted in a lower rate of events from non-culprit lesions (HR 0.50; 95% CI [0.33–0.75]). Conclusion: The introduction of new guidelines improved the prescription status and lipid profile in ACS patients. Guideline-recommended more intensive lipid-lowering therapy may decrease events from non-culprit lesions in ACS patients.