OBJECTIVE: This study aimed to determine the effectiveness of a physical therapist-designed program tailored to axillary web syndrome (AWS) in women after breast cancer surgery. METHODS: A prospective, single-center, assessor-blinded, randomized controlled trial was conducted at the Physiotherapy in Women's Health Research Unit of the Alcalá University (Madrid, Spain). Ninety-six women with AWS were assigned to the physical therapy group (manual lymph drainage [MLD] using resorption strokes and arm exercises as if performing median nerve neurodynamic glide exercises with no neural loading; n = 48) or the control group (standard arm exercises; n = 48), with both groups receiving treatment 3 times a week for 3 weeks. Both interventions included an educational component. RESULTS: Compared with the control group, the physical therapy group showed significant and clinically relevant improvements in the primary outcome (self-reported pain intensity) at the primary and 3-month follow-ups. Significant and clinically relevant differences between groups were also found in the secondary outcomes (shoulder active range of motion, shoulder disability, and physical and functional aspects of health-related quality of life) at the primary follow-up and in the secondary outcomes as well as the trial outcome index at the 3-month follow-up. No significant differences were found at the 6-month follow-up in either primary or secondary outcomes. CONCLUSION: The physical therapy program tailored to AWS was found to be effective for AWS symptoms in women after breast cancer surgery, both immediately after the program and after 3 months. IMPACT: To our knowledge, this is the first appropriately designed study to demonstrate the effectiveness of MLD with progressive arm exercises for AWS. Clinicians and health service providers should consider how to provide survivors of breast cancer with AWS the opportunity to participate in physical therapy programs, including MLD with progressive arm exercises. LAY SUMMARY: For axillary web syndrome following breast cancer surgery, a physical therapist can design a treatment program including manual lymph drainage and progressive arm exercises, which has been shown to result in reduced pain and improved motion compared with standard arm exercises.