PURPOSE: To investigate the effectiveness of a clinical and home-based, nurse-led physical activity program (PAP) and simple lymphatic drainage (SLD) in the prevention of breast cancer-related lymphedema. METHODS: A total of 52 breast cancer patients were randomized to either a PAP and SLD program (n = 25) or a control group (n = 27). Patients in both groups were also provided training for lymphedema. The PAP and SLD were administered through home visits by the investigators, twice a week for six weeks, in the intervention group. The control group did not undergo intervention. The circumference of the upper extremity, symptom severity, and physical function were measured in both groups. RESULTS: The upper extremity circumference increased by about two times from the baseline, in the control group, especially in the sixth week (p < 0.05). Lymphedema-related symptom severity scores were found to decrease significantly in the intervention group, compared to those at the baseline (p < 0.05). CONCLUSION: It was recommended that PAP and SLD, with a follow-up program, be used for patients who planned to undergo breast cancer surgery, starting from before surgery and continuing until after, to prevent breast cancer-related lymphedema.