BACKGROUND: The management of irreparable massive or full-thickness 2-tendon rotator cuff tears in active patients with minimal glenohumeral arthritis remains a difficult challenge for the treating surgeon. Many different treatment options, with varied success, have been proposed. HYPOTHESES: (1) Patients undergoing reconstruction of irreparable massive or full-thickness 2-tendon rotator cuff tears by dermal tissue matrix xenograft would demonstrate improvements in pain, range of motion, strength, and subjective functional outcomes. (2) Postoperative ultrasonography would demonstrate intact repairs at a minimum 2-year follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-six patients (27 shoulders) underwent reconstruction of irreparable massive or full-thickness 2-tendon rotator cuff tears by dermal tissue matrix xenograft. Pain level (scale 0-10, 10 = severe pain), active range of motion, and supraspinatus and external rotation strength were assessed. Subjective outcome measures included American Shoulder and Elbow Score (ASES) and Short Form-12 (SF-12) score. Clinical and radiographic analyses were performed at an average 32-month follow-up period (minimum 2-year follow-up). Ultrasound imaging (static and dynamic) of the operative shoulder was performed at final follow-up to assess the integrity of the construct. RESULTS: Mean patient age was 60 years. Mean pain level decreased from 5.1 to 0.4 (P = .002). Mean active forward flexion and abduction improved from 138.8° to 167.3° (P = .024) and 117.9° to 149.3° (P = .001), respectively. Supraspinatus and external rotation strength improved from 7.2 to 9.4 (P = .001) and 7.4 to 9.5 (P = .001), respectively. Mean ASES improved from 62.7 to 91.8 (P = .0007), and mean SF-12 scores improved from 48.4 to 56.6 (P = .044). Twenty-one patients (22 shoulders) returned for a dynamic and static ultrasound of the operative shoulder at a minimum 2-year follow-up. Sixteen patients (73%) demonstrated a fully intact tendon-graft reconstruction, 5 patients (22%) had a partially intact reconstruction, and 1(5%) had a complete tear at the graft-bone interface caused by suture anchor pullout as a result of a fall. There were no cases of infection or tissue rejection. CONCLUSION: Active patients with massive or 2-tendon rotator cuff tears with minimal glenohumeral arthritis continue to be a subset of the population for whom there is no current standard of care. Results suggest that the use of porcine xenograft may be an effective means by which to treat these patients.