Background: We aimed to evaluate the role of B-type natriuretic peptide (BNP) in assessing severity of coronary artery disease by SYNTAX score (SS) II in a prospective study among ST elevation acute coronary syndrome (ACS) patients. Methods: One thousand and six patients with ST elevation myocardial infarction (STEMI) who admitted for primary percutaneous intervention were included. The patients were divided into two groups according to SS II values (≤32 and >32). The independent predictors of high SS II were investigated, and the best cutoff value of BNP, high-sensitivity C-reactive protein (hs-CRP), peak troponin I, and hemoglobin level in predicting high SS II was determined.Results: There was a positive correlation between BNP, white blood cell, hs-CRP, fasting blood glucose, peak troponin I, and SS I. SS II and hemoglobin were negative, but other parameters were positively correlated. High SS II group independent predictors of hypertension, diabetes mellitus, smoking, multivessel disease, high Killip class, BNP, peak troponin I, hemoglobin, and hs-CRP levels were found in STEMI patients. The value of BNP >87.15 pg/ml with 59% sensitivity and 77% specificity (area under the curve [AUC]: 0.722 [95% confidence interval [CI]: 0.689–0.756], P < 0.001), hs-CRP >10.85 mg/dl with 64% sensitivity and 64% specificity (AUC: 0.685 [95% CI: 0.65–0.72], P < 0.001), peak troponin I >77.83 ng/mL with 68% sensitivity and 63% specificity (AUC: 0.704 [95% CI 0.67–0.738], P < 0.001), and hemoglobin >16.75 g/dL with 4% sensitivity and 97% specificity (AUC: 0.345 [95% CI: 0.309–0.382] P < 0.001) independently predicted high SS II group. Conclusion: Serum BNP level was independently associated with the severity of coronary atherosclerosis in patients with ACS together with multivessel disease, left ventricular ejection fraction, hs-CRP, and troponin. Therefore, BNP assessment gives additional prognostic information for early risk stratification of patients with ACS.