Background Interleukin (IL)-10, IL-6 and their ratio (IL-6/IL-10) play an important role in the risk of developing coronary artery disease, and may correlate with its outcomes. Few clinical trials have investigated the prognostic impact of these factors on long-term cardiovascular events in patients presented with chest pain. Methods A prospective study was performed on 566 patients admitted with chest pain and identified mild to moderate coronary artery lesions. IL-10, IL-6 and IL-6/IL-10 were measured. Results A total of 511 patients completed the follow-up. The median follow-up time was 74 months. Kaplan-Meier analysis demonstrated a clear increase of the incidence of major adverse cardiac events during the follow-up period in patients with below-median levels of IL-10 (P = 0.006) and above-median levels of IL-6/IL-10 (P = 0.012). Multivariate Cox proportional hazards analysis indicated the IL-10 levels to be strong independent predictors after adjustment for underlying confounders. Conclusions Elevated IL-10 levels are associated with a more favorable long-term prognosis in patients with chest pain and mild to moderate coronary artery lesions. IL-10 could be used for early risk assessment of long-term prognosis.