To decrease the gastric cancer related mortality rate, endoscopic screening is widely performed in Korea. However, a precise method for identifying those at a high risk of gastric neoplasms has not been established. This study aims to evaluate serum pepsinogen (PG) levels for risk assessment of gastric neoplasms. Between August 2014 and March 2016, a total of 398 subjects, including 87 with gastric neoplasms, were enrolled in this study. On the basis of the serum PG I/II ratio, the enrolled subjects were classified into 4 groups: group A, PG I/II ratio >4; group B, >3 and ≤4; group C, >2 and ≤3; group D, ≤2. Compared with group A, a stepwise increase in the risk of gastric neoplasm was observed from group B [odds ratio (OR) = 9.9, 95% confidence interval (95% CI) = 4.0–24.4] to group C (OR = 20.9, 95% CI = 8.7–50.5) to group D (OR = 37.3, 95% CI = 14.3–97.4). The optimal cutoff value of the serum PG I/II ratio for predicting gastric neoplasms was 4.5, with a sensitivity of 97.7% and a specificity of 57.6%. A decrease in the serum PG I/II ratio was strongly associated with an increased risk of gastric neoplasms. The serum PG I/II ratio can be used to identify those at a high risk of gastric neoplasms in Korean population.