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Background: Our study aims to analyze the association between Lauren's classification and gastric adenocarcinoma prognosis using comprehensive statistical analyses., Methods: According to the selection criteria, patients were included from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression, propensity score matching, and a multivariate competing risk model were used to investigate the association between Lauren's classification and prognosis. Subgroup analysis was used to investigate the role of confounding factors on the association between Lauren types and prognosis., Results: After exclusion, a total of 20,218 patients from the SEER database were included, with 14,374 intestinal types and 5,844 diffuse types. The univariate Cox regression analysis revealed that the diffuse type had a poorer cancer-specific survival (CSS) rate [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.38-1.50]. After adjusting for confounding variables, the diffuse type also showed a higher risk of cancer-specific death (HR, 1.20; 95% CI, 1.15-1.20). Sensitivity analysis showed that after propensity score matching, the diffuse type had a poorer CSS rate (HR, 1.23; 95% CI, 1.10-1.36), and the competing risk model further validated these results [subdistribution HR (SHR), 1.32; 95% CI, 1.23-1.41]. Moreover, subgroup analysis demonstrated stable results in the subgroups, except for patients with T1 stage (HR, 1.06; 95% CI, 0.87-1.28) and a tumor size <2 cm (HR, 1.00; 95% CI, 0.83-1.21)., Conclusions: Diffuse-type gastric adenocarcinoma had an overall poorer prognosis compared to the intestinal type. However, in patients with T1 stage and tumor size <2 cm, the diffuse type had a comparable survival rate with the intestinal type., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7953). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)