Background/Aims: While Helicobacter pylori (HP)-negative gastric cancer is frequently reported, little is known about the predictors for detecting HP-negative early gastric cancer (EGC). We aimed to evaluate the predictors for the detection of HP-negative EGC. Methods: We retrospectively reviewed 13,477 consecutive asymptomatic cases where upper endoscopy was performed by nine physicians from April 2017 to March 2019 and analyzed the detection rate of high-risk lesions (HRLs), including EGC, tubular adenoma, and lymphoma, according to the status of HP infection. The observation time was corrected for multiple regression analyses. Results: For all physicians, the average observation time for screening HP-eradicated and -naïve patients was shorter than that for screening HP-positive patients (p<0.05). Multiple regression analyses revealed that the observation time in the three groups was an independent predictor for detecting HRLs in HP-eradicated patients (p=0.03106, 0.01263, and 0.02485, respectively), while experience of endoscopy was an independent predictor for detecting HRLs in HP-naïve patients (p=0.02638). Conclusions While observation time during screening endoscopy was a quality indicator for detecting HRLs in HP-eradicated patients, experience of endoscopy was a quality indicator for detecting HRLs in HP-naïve patients.