BACKGROUND: Cisplatin plus pemetrexed is considered the standard of care for the first-line treatment of patients with advanced non-squamous non-small-cell lung cancer (NSCLC). However, little is known about the efficacy and safety of this regimen in Japanese patients in a daily clinical setting. METHODS: We retrospectively analyzed 40 patients who received cisplatin (75 mg/m/(2)) and pemetrexed (500 mg/m(2)) as a first-line treatment for advanced non-squamous NSCLC. RESULTS: Recorded Grade 3 or 4 hematological toxicities included neutropenia in 7 cases (17.5%), leukopenia in 5 cases (12.5%), anemia in 1 case (2.5%), thrombocytopenia in 1 case (2.5%), and febrile neutropenia in 1 case (2.5%). Grade 3 or 4 nonhematological toxicities included anorexia in 3 cases (7.5%), infection in 1 case (2.5%), rash in 1 case (2.5%), and increased transaminase expression in 1 case (2.5%). Therefore, the adverse events were mostly mild. There were no treatment related deaths. The overall response rate was 37.5%, median progression free survival was 5.6 months, and median overall survival (OS) was 18.8 months. In an epidermal growth factor receptor (EGFR) mutation status subgroup analysis, the median OS of patients with wild-type EGFR or unknown status (n=28)was 16.8 months. CONCLUSION: Cisplatin plus pemetrexed was well tolerated as a first-line treatment and effective in Japanese patients with advanced non-squamous NSCLC.