The purpose of this study is to investigate adverse prognostic CT findings in patients with advanced-stage lung adenocarcinoma who are receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy as first-line therapy. We included 199 patients (71 men and 128 women; mean ± SD age, 64.3 ± 11.2 years) with stage IIIB or IV lung adenocarcinoma who received first-line EGFR-TKI therapy between January 2009 and December 2015. Clinical findings and imaging parameters on CT images obtained before TKI therapy were analyzed, including tumor size, TNM category according to the seventh edition of the American Joint Committee on Cancer lung cancer TNM staging system, tumor type, the presence of cavity or necrosis, pleural effusion, and metastasis to pleura, lung, and distant organs. Response evaluation was performed according to the Response Evaluation Criteria in Solid Tumor version 1.1 guidelines. Correlation of clinical and radiologic findings with durations of progression-free survival (PFS) and overall survival (OS) was evaluated using a Cox proportional hazard model. Pleural effusion (hazard ratio [HR], 2.095; 95% CI, 1.394-3.147; p < 0.001) and an N2 or N3 tumor category (HR, 2.145; 95% CI, 1.280-3.594; p = 0.004) were significantly associated with a short PFS duration in multivariate analysis. Older age (HR, 1.040; 95% CI, 1.014-1.067; p = 0.002), an N2 or N3 tumor category (HR, 2.427; 95% CI, 1.068-5.518; p = 0.034), pleural effusion (HR, 1.903; 95% CI, 1.105-3.276; p = 0.020), and distant metastasis (HR, 2.795; 95% CI, 1.356-5.765; p = 0.005) were associated with a short OS duration in multivariate analysis. Pre-TKI therapy CT findings of pleural effusion and high N-category tumors are associated with short durations of PFS and OS in patients with lung adenocarcinoma who are receiving EGFR-TKI therapy.