Background: Many lung cancer patients with epidermal growth factor receptor (EGFR) mutations benefit from tyrosine kinase inhibitors (TKIs). However, patients with EGFR exon 20 mutations usually have worse response rates than other types of EGFR mutations. Here we investigated how different mutation subtypes of EGFR exon 20 affected the prognosis. Methods: Clinical and genomic data from 3 studies (MSKCC2020, MSKCC2021, and OncoSG) of patients with lung adenocarcinoma (LUAD) were reviewed (n = 1,001). Four hundred and seventeen patients harbored EGFR mutations and 52 of them had EGFR exon 20 mutations. The correlation of mutation subtypes with OS data was analyzed using R package. Results: In lung cancer patients with EGFR mutations (n = 417), 52 of them (12.5%) had a total of 64 EGFR exon 20 mutations, and could be categorized into 16 different subtypes, with top 5 subtypes being T790M (n = 28), S768I (n = 8), C797S (n = 7), A767_V769dup (n = 6) and S768_D770dup (n = 3). Patients with S768I (p = 0.0038) and A767_V769dup (p = 0.03) were found to have significantly worse OS than patients without these mutations by log-rank test. EGFR T790M, which was the most prevalent exon 20 mutation in these patients, did not present significant correlation in survival analysis. Conclusions: Although patients with EGFR exon 20 mutations accounted for only about 5% LUAD patients, and had worse response rates in general, certain subtypes had significantly different prognoses compared with other subtypes.