Background: Gastric cancer (GC) in Guatemala is the second most common cancer diagnosis and the second leading cause of cancer death in both sexes. It is difficult to determine the exact incidence rate of H. pylori infection‐negative gastric cancer (HPIN‐GC) because H. pylori detection rates decrease with the progression of gastric atrophy and intestinal metaplasia. The aim of this study was to evaluate the incidence, clinicopathologic characteristics, treatment modalities and outcomes. Methods: A retrospective review of the medical records of 210 pts with histological diagnosis of gastric cancer evaluated at the General Hospital of Diseases from the Guatemalan Social Security Institute (IGSS) from January 2010 to December 2018. Helicobacter pylori infection status was evaluated by histology, a rapid urease test Current H. pylori infection was defined as positive results from histology. Overall survival was estimated by Kaplan Meier method and compared by Log-rank test. P value < 0.05 was considered significant. Results: The rate of HPIN‐GC occurrence was 36% (n = 76). Sex, age, location of the tumor, Lauren’s classification and treatment modalities were not different according to H. pylori infection status. However, HPIN‐GC had a more advanced pT classification (T3/T4; 58 vs 28%, p=.019) and a more advanced stage (more than stage I; 64 vs 44%, p=.033) than H. pylori‐positive gastric cancer. Treatment modalities: 22% gastrectomy, 24% palliative care, 54% systemic chemotherapy at any time of disease course, 33% initial palliative surgery (derivative o gastrectomy), gastrectomy at any time in 16% (n 7). For those patients who received systemic chemotherapy (n 113) objective response rate was 38% and disease control rate 66%.Median OS was 26 months: 47 m for localized, 18 for locally advanced, and 8 m for advanced disease (P=.0001). Only 17% of patients received second line chemotherapy and 4% a third line. Conclusions: At least 36% cases of gastric cancer were H. pylori negative. HPIN‐GC looks like to have a poorer prognosis than H. pylori‐positive cases. Chemotherapy can be offered to less than a half of patients. the earliest stages are associated with better survival.