Background <p>Shoulder-hand syndrome (SHS) is a common upper limb complication following stroke. It is associated with poor functional recovery of the upper limb and reduced mobility. Both kinesiology tape (KT) and manual lymphatic drainage (MLD) are considered effective interventions for treating pain and swelling associated with SHS. However, there is currently no research examining the limitations and safety profile of combining K-tape with MLD for SHS management. This study aims to investigate the efficacy of KT combined with MLD in patients with post-stroke shoulder-hand syndrome.</p> Methods <p>This study will be a prospective, single-center, randomized, factorial, controlled clinical trial. This exploratory randomized controlled trial aimed to investigate the efficacy of MLD combined with KT for post-stroke SHS. This study used a blinded design. Ninety-six patients with post-stroke SHS are randomly divided into four groups: (<i>n</i> = 24 per group): Experimental Group 1: Conventional Rehabilitation (CR) + KT, Experimental Group 2: Conventional Rehabilitation (CR) + MLD, Experimental Group 3 (EG3): KT + MLD, Control Group: CR alone. All participants will receive CR as the baseline intervention. All subjects are first‑ever stroke patients diagnosed with unilateral limb paralysis by CT and/or MRI and meet the diagnostic criteria for SHS.</p> <p>The informed consent process is carried out by a trained researcher not involved in the patients’ clinical care in a private room. Therapists participating in this study must hold a rehabilitation therapist qualification. Unified training will be provided to the treating therapists on MLD, KT, and conventional rehabilitation techniques. This study is conducted at the Army Specialized Medical Center. The Army Specialized Medical Center is a tertiary Grade A hospital located in Southwest China. In China’s hierarchical medical system, tertiary Grade A hospitals represent the highest level in the hospital classification system. Outcome measures will be assessed at four time points: baseline (T0), 4&#xa0;weeks after initiating the intervention (T1), 3&#xa0;months post-treatment (T2), 6-month follow-up (T3). The primary endpoints will be as follows: pain intensity measured by the Visual Analogue Scale (VAS) at T1, volume difference between the affected and unaffected upper limbs at T1. Secondary endpoints will include the following: upper limb motor function assessed by the Fugl-Meyer assessment for upper extremity (FMA-UE), activities of daily living evaluated using the modified Barthel index (MBI), joint range of motion (ROM) measurements, quality of life measured by the Stroke-specific quality of life scale (SS-QOL). Safety is assessed by monitoring vital signs (blood pressure and heart rate) before and after treatment, examining skin integrity at the tape application site for any adverse reactions (e.g., redness, rash), and recording any patient-reported increases in pain or other unexpected discomfort potentially related to the intervention.</p> Discussion <p>The efficacy of personalized rehabilitation therapy prescription interventions will be assessed through changes in primary and secondary outcome measures at the 4-week intervention point and during the 12-week follow-up period. To analyze whether MLD combined with KT for post-stroke shoulder-hand syndrome is superior to conventional rehabilitation in terms of pain, swelling, and motor function.</p> Trial registration <p>Clinical Trial Registry-China ChiCTR2300074140.&#xa0;<a href="https://www.chictr.org.cn/">https://www.chictr.org.cn/</a>. First submitted on 31 July 2023.</p>