Limited options exist for the treatment of massive rotator cuff tears (MRCTs). Surgical repair may be technically challenging and require prolonged rehabilitation with variable outcomes. The present study was designed to assess the safety and efficacy of an arthroscopically-deployed inflatable biodegradable subacromial spacer balloon (InSpaceTM, OrthoSpace, Israel) as an alternative to partial repair in patients with MRCTs. A non-inferiority, prospective, single-blinded, multicenter, randomized, controlled, pivotal study was conducted to compare the outcomes of arthroscopic subacromial balloon spacer implantation to partial repair in the treatment of MRCTs. Patients ≥ 40-years of age with full thickness MRCTs (≥ 5 cm, ≥ 2 tendons) were included. Baseline and follow-up data were collected to identify patients that had reached a primary composite endpoint consisting of the minimal clinically important difference (MCID) for the Western Ontario Rotator Cuff (WORC) score (275 points) and American Shoulder and Elbow Society (ASES) score (6.4 points) by 6-weeks and maintained at 12-months without subsequent secondary surgical intervention (SSSI) or serious adverse device effects (SADEs). 184 patients were randomized, 176 (88/group) of which completed the required 12-month follow-up per protocol. At 12-months, 45 (51%) patients in the spacer implant group and 35 patients (39.8%) in the partial repair group, had reached and maintained the primary composite endpoint, corresponding to a difference between groups of 11.4% (non-inferiority margin 10%; p = 0.0049). Additionally, the spacer implant group demonstrated superior improvement (p = 0.0224) when evaluating the following combined efficacy timepoints of ASES score at 6-weeks and WORC score at 12-weeks, both maintained at 12-months in the absence of SSSI or SADEs, compared to the partial repair group. Arthroscopic subacromial balloon spacer implantation is a viable alternative to partial repair in the treatment of symptomatic MRCTs with comparable clinical outcomes at one year.