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Abstract Background Osimertinib is associated with a relatively high frequency of drug‐induced interstitial lung disease (D‐ILD), and transient asymptomatic pulmonary opacities (TAPO) have been reported to occur during osimertinib administration. The frequency of TAPO during first‐line treatment and the pros and cons of osimertinib continuation is unknown. Methods This was a multicenter, retrospective study. The purpose of this study was to research the frequency of TAPO and to evaluate osimertinib continuation in first‐line therapy. We also evaluated progression‐free survival (PFS) including subgroup analysis. Results From August 2018 to December 2020, 133 patients were enrolled into the study. The median observation period was 23.2 months (0.3–48.3 months). Thirty patients (22.6%) experienced D‐ILD events, including 16 patients (12.1%) with CTCAE grade 1, five patients (3.8%) with grade 2, and nine patients (6.7%) with grade 3 and above D‐ILD. Among the patients with grade 1 D‐ILD, 11 cases (8.3%) of TAPO were observed, and all patients succeeded in osimertinib continuation. The TAPO images were characterized by localized patchy opacities (73%). The median PFS was 22.6 months (95% confidence interval [CI]: 17.8–28.7 months). Patients with TAPO had a significantly longer PFS than patients with non‐TAPO D‐ILD in the multivariate analysis. Conclusions This study showed that grade 1 D‐ILD might include TAPO and that patients with TAPO might have good PFS. We need to consider the possibility of osimertinib continuation when lung opacities appear.