PROJECT SUMMARY Subacromial pain, a generic term used to describe pain with disorders of structures within the subacromial space, is the most common reason for shoulder-related visits to primary care and has a high one-year prevalence. Patients with subacromial pain frequently complain of difficulty using the arm, impaired lifting, and limited exercise tolerance. Strengthening is a clinically relevant outcome in patients with subacromial pain. However, the high loads required for strengthening exacerbate pain and stress the rotator cuff tendons. Therefore, clinical practice guidelines recommend strengthening with low intensity and high frequency, but this combination often results in undertraining exercise prescriptions and lasting weakness. Blood flow restriction training (BFRT) is emerging as a novel adjunct treatment to address muscle weakness. It consists of strengthening exercises while an inflatable cuff restricts blood flow at the extremity. It is popular with athletes because it promotes muscle hypertrophy. It is also highly appealing as a rehabilitation strategy because it requires low external loads for strengthening. BFRT could have a tremendous positive impact on the recovery of patients with subacromial pain, but research is lacking. Our long-term goal is to conduct a large-scale efficacy trial of BFRT in patients with subacromial pain. As a critical step toward our long-term goal, this proposal is a pilot randomized trial to test trial procedures, safety and feasibility of the intervention, and preliminary efficacy of BFRT. Our pilot trial will be double masked (investigator & outcome assessor), include two parallel arms (active or sham BFRT), and two endpoints (after 16 BFRT sessions, primary endpoint; and after six months, secondary endpoint). This design is robust because it controls the non-specific effects of receiving BFRT (sham). The first aim tests recruitment, randomization, participant masking, retention, and data collection procedures. The second aim determine the safety and feasibility of the interventions (active BFRT and sham BFRT). The third aim describe the effect of active BFRT on clinical outcomes (shoulder strength, patient-reported outcomes, shoulder performance, muscle hypertrophy, and tendon thickness & elasticity). This application is innovative because: a) applies BFRT in a clinical population with subacromial pain; b) has clear objectives, analytic plans, and criteria to establish the success of the trial procedures, safety, and feasibility outcomes; and c) uses comprehensive outcomes to evaluate clinical recovery. The popularity of BFRT among professional athletes favors quick transitions to clinical applications even without support from high-quality research. Completing this preliminary trial will demonstrate that we have the capacity and capability to conduct and deliver a large-scale efficacy trial as planned. Collectively, this line of research will directly impact clinical practice.