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Objective: To elucidate the potential benefits of combining radiotherapy and epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) for individuals with Stage IV lung adenocarcinoma (LUAD) harboring either exon 19 deletion (19‐Del) or exon 21 L858R mutation (21‐L858R). Methods: In this real‐world retrospective study, 177 individuals with Stage IV LUAD who underwent EGFR‐TKIs and radiotherapy at Shandong Cancer Hospital from June 2012 to August 2017 were included. The main focus of this real‐world study was overall survival (OS). Results: The clinical characteristics of patients with Stage IV LUAD harboring 19‐Del were similar to those harboring 21‐L858R (p > 0.05). Overall, the patients had a median OS (mOS) of 32.0 months (95% confidence interval [CI]: 28.6–35.5). Subsequently, multivariate analysis indicated that both EGFR mutations and thoracic radiotherapy were independent predictors of OS (p = 0.001 and 0.013). Furthermore, subgroup analysis highlighted a longer OS for the 19‐Del group compared to the 21‐L858R group, especially when EGFR‐TKIs were combined with bone metastasis or thoracic radiotherapy (mOS: 34.7 vs. 25.1 months and 51.0 vs. 29.6 months; p = 0.0056 and 0.0013, respectively). However, no significant differences were found in OS when considering patients who underwent brain metastasis radiotherapy (mOS: 34.7 vs. 25.1 months; p = 0.088). Conclusions: Patients with Stage IV LUAD harboring 19‐Del experience a notably prolonged OS following combined therapy with EGFR‐TKIs and radiotherapy, while this OS benefit is observed despite the absence of substantial differences in the clinical characteristics between the 19‐Del and 21‐L858R groups. [ABSTRACT FROM AUTHOR]