Abstract Background The evidence of adherence to statin decreasing risk of major adverse cardiovascular events (MACEs) is still lack among patients discharged with acute coronary syndrome (ACS). Our objective is to determine the relationship between six-month adherence to statins and subsequent risk of MACEs in patients discharged with ACS. Methods Using two prospective registry cohorts (CPACS-1 and -2), we analyzed data from 12,516 consecutive patients with ACS who were prescribed statin at hospital discharge and survived beyond 6 months without recurrent myocardial infarction (MI) or stroke. Adherence to statin was defined as good (using statin at discharge and 6 months without declined dosage) and poor adherence groups (using statin at discharge but declining dosage or stopping at 6 months). We compared the hazard ratios of all-cause mortality and MACE in subsequent 6 months between groups, using Cox-regression models, adjusting for multiple potential confounders. Results Seventy two percent of patients adhered to statin therapy at 6 months. The incident MACE in the poor adherence group was significantly higher than in good adherence group (2.7% vs. 1.8%, p = 0.002). Compared with poor adherence group, the good adherence group showed a 27% lower relative risk of MACE during the 6 month follow up (fully-adjusted hazard ratio (HR) = 0.73; 95%CI: 0.56–0.97). The protective effects of good adherence were similar in groups with different statin dose as well as groups by other baseline clinical characteristics and treatments (p > 0.05 for interaction). Conclusion Our study highlights the importance of adherence to statin therapy in prevention of MACE and clinicians should aim to achieve higher dosage if tolerable. Clinical trial registration CPACS2 was registered on URL: http://www.anzctr.org.au/default.aspx and unique identifier is ACTRN12609000491268 . CPACS1 was not a clinical trial and thus not registered.