Objective To investigate the correlation between plasma interleukin (IL)-22 level and the severity of coronary artery disease and 5-year prognosis in patients with acute myocardial infarction (AMI). Methods A total of 98 AMI patients who underwent emergency percutaneous coronary intervention in Special Medical Center of Strategic Support Force from Oct. 2014 to Dec. 2016 were selected, including 58 cases of ST segment elevation myocardial infarction (STEMI) and 40 cases of non-ST segment elevation myocardial infarction (NSTEMI). Forty patients with normal coronary angiography during the same period were selected for control group. The plasma levels of inflammatory cytokines IL-22, IL-1β, IL-6 and tumor necrosis factor α (TNF-α) were measured by Luminex liquid chip technique. The baseline data and plasma levels of inflammatory cytokines were compared among the 3 groups to analyze the relationship between IL-22 level and other inflammatory cytokines in AMI patients. Pearson correlation analysis and multiple linear regression analysis were used to explore the relationship between plasma IL-22 level and SYNergy between percutaneous coronary intervention with TAXUS^TM and cardiac surgery (SYNTAX) score. Receiver operating characteristic (ROC) curve was used to analyze the prediction ability of some indexes (such as IL-22) for medium-high SYNTAX scores. Binary logistic regression analysis was used to analyze the risk factors of major adverse cardiovascular and cerebrovascular event (MACCE) in patients with AMI within 5 years after discharge. Results There were no significant differences in baseline data such as age, gender or smoking history between the AMI group and control group (all P>0.05). The proportions of patients with family history of coronary heart disease, fasting blood glucose, hypersensitive C reactive protein and brain natriuretic peptide in the STEMI and NSTEMI groups were higher than those in the control group (all P<0.05), while the levels of high density lipoprotein-cholesterol and left ventricular ejection fraction (LVEF) were lower than those in the control group (both P<0.05). The plasma levels of IL-22, IL-1β, IL-6 and TNF-α in AMI patients were significantly higher than those in the control group (all P< 0.05). Plasma IL-22 level was positively correlated with IL-1β (r=0.793, P=0.001), IL-6 (r=0.880, P<0.001) and TNF-α (r=0.840, P<0.001). SYNTAX score was positively correlated with IL-22 (r=0.478, P=0.001), IL-6 (r=0.242, P=0.017), age (r=0.217, P=0.032) and cardiac troponin I (r=0.261, P=0.010), and negatively correlated with LVEF (r=-0.224, P=0.034). Multiple linear regression analysis with SYNTAX score used as dependent variable, IL-22 (β=0.269, P=0.023), age (β=0.236, P=0.016) and LVEF (β=-0.235, P=0.023) were the influence factors of SYNTAX score. The analysis of ROC curve showed that the predictive ability of plasma IL-22 for medium-high SYNTAX scores (area under curve[AUC]=0.760, 95% confidence interval[CI] 0.656-0.863, P=0.001) was higher than that of age (AUC=0.612, 95% CI 0.478-0.746, P=0.112) and LVEF (AUC=0.628, 95% CI 0.485-0.770, P=0.070). There was no correlation between SYNTAX score and plasma IL-22 level and MACCE in patients with AMI within 5 years after discharge. Conclusion Plasma IL-22 level is related to AMI and can reflect the severity of coronary artery disease. It has good predictive value for judging the condition of patients with AMI, but the correlation with the prognosis of patients needs to be further verified.