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Background: We conducted a multicenter, retrospective study on the efficacy and safety of naldemedine in thoracic cancer patients using opioids in clinical practice. Methods: We retrospectively evaluated thoracic cancer patients treated with naldemedine at 10 institutions in Japan. Clinical data of patients administered naldemedine between June 2017 and August 2019 were extracted from electronic medical records. Inclusion criteria were as follows: (i) patients hospitalized for at least seven days before and after naldemedine administration, and (ii) those whose frequency of defecation was entered in the medical records. Results: Forty patients were analyzed, and defecation frequency was observed for at least seven days before and after naldemedine administration. The response rate was 65.0% (95% CI: 50.2%–79.7%). The number of defecations increased significantly after naldemedine administration in the overall population, as well as among only those who defecated <3 times/week before naldemedine administration, and those that were administered ≥30 mg/day of morphine equivalent. Diarrhea was the most common adverse event in all grades, occurring in 11 patients (27.5%), of which 9 (81.8%) were grade 1 or 2. None of the patients experienced grade 4 or higher adverse events. Conclusion: The efficacy and safety of naldemedine for thoracic cancer patients in clinical practice were comparable with those of prospective studies, which suggest that naldemedine may be effective and feasible for most thoracic cancer patients. [ABSTRACT FROM AUTHOR]