Commercially available suture anchors for rotator cuff repairs can differ significantly in architecture and material. Clinical data on their osseous integration and its effect on patient-reported outcomes is scarce. Preclinical investigations indicated a higher rate of osseous integration for the open-architecture design of the Healicoil Regenesorb anchor than the closed-threaded design of the Twinfix (Smith & Nephew). The purpose of this study was to investigate these 2 anchors with different architecture and material to determine their effect on osseous integration and clinical outcomes after rotator cuff repair. A prospective randomized controlled trial was performed from 2014 to 2019. Sixty-four patients (39 females, 25 males) with an average age of 58.7 years who underwent arthroscopic rotator cuff repair by one of 4 board-certified, fellowship-trained surgeons were randomized to receive Healicoil Regenesorb (PLGA/ß-TCP/Calcium Sulfate) or Twinfix Ultra HA (PLLA/HA) anchors. Thirty-two patients had Healicoil anchors implanted, and 32 patients had Twinfix anchors implanted. Of the 64 patients, 51 returned at 24 months for computed tomographic (CT) examination (25 Twinfix and 26 Healicoil) to determine osteointegration of the anchors. Patient-reported outcomes, including Penn Shoulder Score (PENN), Western Ontario Rotator Cuff Index, visual analog scale, EQ-5D, Single Assessment Numeric Evaluation, Global Rating of Change, were collected at baseline, 6 weeks, 3 months, 6 months, 12 months, and 24 months. Ultrasonography was used to assess rotator cuff integrity after 6 months. Two board-certified, fellowship-trained orthopedic surgeons, blinded to the type of anchors, analyzed the CT scans to assess the anchor osteointegration at 24 months using a previously published grading scale. There were no differences in demographics, preoperative outcomes, or baseline characteristics such as tear size, number of anchors, Goutallier classification, or smoking status between groups. There was no difference in osseous integration between the 2 anchors at 24 months (P = .117). Eight patients had rotator cuff retears, of which 2 patients had Twinfix anchors and 6 patients had Healicoil anchors (P = .18). There were no statistically significant differences in patient-reported outcomes or complications between groups. The 2-year PENN scores were 89 with the Twinfix and 88 with Healicoil anchors (P = .55). Despite differences in material and anchor architecture, the rate of healing and patient-reported outcomes were similar between the Twinfix and Healicoil anchor groups. The rate of osteointegration was the same at 2 years.