Midcarpal osteoarthritis is a debilitating wrist pain, and a mainstay treatment is midcarpal fusion. The accepted standard for midcarpal fusion is four-corner fusion, but lately, two-corner fusion (i.e., capitolunate fusion) has gained popularity. This is the first prospective, multicenter, cohort study comparing capitolunate fusion with four-corner fusion for midcarpal osteoarthritis. Patients with scaphoid nonunion advanced collapse or scapholunate advanced collapse wrist of grade 2 to 3 undergoing capitolunate fusion or four-corner fusion between 2013 and 2019 were included. Sixty-three patients (34 with capitolunate fusion, 29 with four-corner fusion) were included. Patient demographics were similar between groups. Patient-Rated Wrist Hand Evaluation questionnaire score, visual analog scale pain score, grip strength, range of motion, and complications were measured at baseline and 3 months and 12 months postoperatively. Complications (i.e., nonunion, hardware migration, conversion to wrist arthrodesis, or arthroplasty) were determined. A significant difference in Patient-Rated Wrist Hand Evaluation or visual analog scale pain score at 3 and 12 months postoperatively between the capitolunate fusion and four-corner fusion groups was not found. There were no differences in grip strength between patient groups preoperatively or 12 months postoperatively. At 12 months postoperatively, capitolunate fusion patients had better flexion compared with that in the four-corner fusion group (p = 0.002); there were no differences in complications and reoperation rates between groups. Capitolunate fusion and four-corner fusion were comparable in terms of functional scores (i.e., Patient-Rated Wrist Hand Evaluation and visual analog scale pain scores) and complication scores. Capitolunate fusion showed favorable wrist mobility compared with four-corner fusion in treatment of midcarpal osteoarthritis. Capitolunate fusion advantages include use of less material, less need for bone-graft harvesting, and easier reduction of the lunate during fixation. Therapeutic, II.