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This study aimed to investigate the effect of lipoprotein(a) (Lp(a)) on major adverse cardiovascular events (MACEs) among individuals with chronic coronary syndrome (CCS) according to ABO blood groups. Two independent cohorts of patients with CCS were included consecutively. Blood groups and Lp(a) levels were measured. Patients with the AB group were excluded due to the small sample size. In the exploratory cohort (n = 7611), 560 MACEs were recorded over a mean follow-up of 54.80 months. Stratification analysis revealed that the relationship of elevated Lp(a) levels with prognosis was more pronounced in patients with blood group A or B. Patients with blood group A or B plus medium Lp(a) (HR, 1.93, 95% CI: 1.24-3.01) or high Lp(a) (HR, 2.06, 95% CI: 1.32-3.24) concentrations had a significantly higher risk of MACEs compared to those with blood group O and low Lp(a) levels. Similar results were obtained in the confirmatory cohort (n = 7916). In conclusion, our data demonstrated for the first time a more prominent association between Lp(a) and adverse outcomes in CCS patients with non-O blood group compared to those with blood group O, suggesting that ABO blood group measurement may be clinically useful for decision-making in Lp(a) intervention.