<b><i>Background:</i></b> The factors associated with the pathogenesis of <i>Helicobacter pylori</i>-uninfected undifferentiated-type early gastric cancer (HPUGC) remain unclear. This study compared patient characteristics, including medical history and alcohol/tobacco use, of HPUGC patients with characteristics of patients with <i>H. pylori</i>-positive undifferentiated-type early gastric cancer (HPPGC) to clarify and gain understanding on those differences that could play a role in the pathogenesis. <b><i>Methods:</i></b> This retrospective study included 282 patients who were treated endoscopically from March 2005 to March 2014. This cohort consisted of 232 patients with HPPGC (82.3%) and 50 patients with HPUGC (17.7%). Patient characteristics were analyzed by subgroups of HPUGC vs. HPPGC, with comparisons for age, gender, cancer history, comorbidity of lifestyle diseases requiring medication (hypertension, type 2 diabetes, and dyslipidemia), cumulative amount of alcohol consumption, and smoking history (Brinkman index [BI]). <b><i>Results:</i></b> HPUGC patients were typically younger, had less frequent hypertension, and had higher BI values (<i>p</i> &#x3c; 0.05 for all parameters). In a younger non-hypertensive subgroup, the OR for high BI (BI ≥340) in the HPUGC group vs. HPPGC group was 5.049 (95% CI 2.458–10.373, <i>p</i> &#x3c; 0.0001). <b><i>Conclusions:</i></b> The investigation of clinical factors identified smoking history as being possibly contributing to the pathogenesis of HPUGC. Future research is necessary at the cellular and genetic levels.