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Background: In clinical practice, the management of cancer-related anorexia/cachexia syndrome (CACS) is a great challenge. We conducted an observational study to find the effectiveness and safety of megestrol acetate (MA) for the treatment of CACS. Patients and Methods: One hundred patients of advanced cancer were randomly assigned in the study. Patients received MA 160 mg/oral twice daily. The duration of treatment was 8 weeks. Results: The analysis of the study group demonstrated a statistically significant increase from baseline in body weight (P ≤ 0.01), quality of life (P = 0.02), appetite (P = 0.01), and the Eastern Cooperative Oncology Group performance status (P = 0.03). Conclusion: We concluded that MA is effective and safe in the treatment of CACS.