Background: Helicobacter pylori (H. pylori) infection status in Indonesia might be higher than the actual prevalence. A comprehensive epidemiologic study is necessary to explore infection susceptibility by demographic characteristics, especially between Indonesia’s Eastern and Western regions. Methods: We included our recent survey and data from our previous studies with 1,172 endoscopic examinations from 19 cities throughout Indonesia from January 2014 to March 2017. H. pylori infection was diagnosed based on the combination of four different tests. Using a criterion of one positive result between four tests, we found that 190 subjects (190/1,158; 16.4%) were H. pylori positive. A total of 939 subjects were analyzed for risk factors of sociodemographic characteristics to H. pylori infection. Results: Prevalence was slightly higher in the Eastern region compared with the Western region of Indonesia (79/277; 59.4% vs. 54/529; 40.6%). Living in the Eastern region imposes a higher risk of infection (OR 5.33, 95%CI 1.17–24.26). Timor ethnicity had the highest prevalence (15/28; 53.6%), followed by Buginese ethnic (21/74; 28.4%), and Papuan ethnic (18/64; 28.1%) in the Eastern region. As an ethnicity with a high prevalence (37/109; 33.9%), Batak was an outlier among the low prevalence areas in the Western region. In general, age, living in the Eastern region, Batak ethnicity, Protestant, Catholic, and alcohol drinking were independent risk factors associated with H. pylori infection in Indonesia (OR 1.03, 95%CI 1.02–1.05; OR 5.33, 95%CI 1.17–24.26; OR 5.89, 95%CI 1.58–21.94; OR 5.47, 95%CI 2.16–13.86; OR 5.05, 95%CI 1.43–17.80; OR 2.30, 95%CI 1.14–4.61, respectively). Conclusions: Several ethnicities and habits were concluded to increase the risk of infection as the interaction of host, agent, and environment is inseparable in affecting disease susceptibility.