BACKGROUND AND AIMS: The detection of gastric intestinal metaplasia (GIM), gastric intraepithelial neoplasia (GIN), and early gastric cancer (EGC) using white light endoscopy (WLE) is unsatisfactory. This study assessed the value of optical enhancement combined with magnification endoscopy (ME-OE) versus WLE for detecting GIM, GIN and EGC. METHODS: Patients at high risk for gastric cancer were randomly assigned to ME-OE group or WLE group at 1: 1. Suspicious GIM, GIN and EGC lesions were targeted biopsied in both groups. The diagnostic yield, diagnostic efficacy and agreement of suspicious lesions were compared between the two groups. RESULTS: A total of 285 patients were finally analyzed. The per-patient diagnostic yields of GIM/GIN/EGC were 36.6% and 23.8% in ME-OE and WLE groups, respectively (P = 0.018). The per-lesion diagnostic yield of GIM/GIN/EGC in ME-OE group was higher than that in WLE group (66.7% vs 48.7%, P = 0.017). Sensitivity (82.8% vs 54.3%, P = 0.003), specificity (84.2% vs 81.4%, P = 0.738), positive predictive value (88.9% vs 70.4%, P = 0.038), negative predictive value (76.2% vs 68.6%, P = 0.419), and accuracy (83.3% vs 69.2%, P = 0.028) for GIM were compared between the two groups. The intra-observer agreements of experienced endoscopists were excellent for ME-OE (κ = 0.81, κ = 0.83) and good for WLE (κ = 0.63, κ = 0.62). The inter-observer agreements of experienced endoscopists were good for both groups, with κ-values of 0.75 and 0.61, respectively. CONCLUSION: ME-OE showed better performance for detecting GIM than WLE in high-risk populations.