We investigated risk factors for gastric cancer (GC) and effect of annual endoscopic screening on detection and treatment modality of GC. Asymptomatic adults who underwent upper endoscopy during health checkups at Seoul National University Hospital Healthcare System Gangnam Center were enrolled. We compared clinicopathologic characteristics of GC according to screening interval (repeated vs. infrequent, annual vs. biennial). After age- and sex-matching, relative risk was computed by hazard ratio (HR) using Cox proportional regression with multivariate adjustment. Of the 58,849 subjects who received screening endoscopy, 277 (0.47%) were found to have GC. Intestinal type comprised 55.4% (102/184) followed by diffuse type (n = 65, 35.3%). Age ≥ 50 years, family history and smoking independently increased the risk of GC for both types, whereas male gender [HR = 4.81, 95% confidence interval (CI): 2.72-8.03] and intestinal metaplasia (IM) (HR = 10.87, 95% CI: 3.36-22.30) were significant predictors for intestinal type only. Proportion of early gastric cancer (EGC) was 98.6% (71/72) in annual screening group and 80.7% (46/57) in biennial screening group (p < 0.01). In the former, tumor size was smaller (1.7 ± 1.3 vs. 2.3 ± 1.8 cm; p < 0.01] and proportion of intramucosal cancer was larger (75.0 vs. 56.1%; p = 0.04). Endoscopic resection was performed more frequently in annual screening group (56.9 vs. 33.3%; p = 0.02). IM along with male gender and older age was a strong risk factor for intestinal type GC. Annual screening group improved detection of early-stage and endoscopically treatable GC suggesting that intensive screening and surveillance may be useful for high-risk subpopulations with epidemiologic risk factors or premalignant lesions such as IM.