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Background: In the past decade, there has been a trend toward open reduction and internal fixation of unstable distal radial fractures. There are now more than thirty different implant designs specific for the fixation of distal radial fractures. A multicenter prospective study of a case series was conducted to determine the efficacy of the operative management of distal radial fractures stabilized with 2.4-mm locking plates.Methods: One hundred and fifty patients were entered into the study over a two-year period. The mean age of these patients was fifty-one years, and the cohort included eighty-eight women and sixty-two men. Eighty-six patients sustained a low-energy injury. Seventy-one percent of the fractures in the series were intra-articular and were Type C according to the Müller-AO Comprehensive Classification. The follow-up evaluations, which were conducted at six weeks, six months, one year, and two years, included assessments of pain, motion, grip strength, and standard radiographs. Gartland and Werley scores were recorded at six months and one and two years, and Disabilities of the Arm, Shoulder and Hand (DASH) scores were recorded at one and two years.Results: One hundred and twenty-five patients (83%) had a complete follow-up at six months; 121 (81%), at one year; and 117 (78%), at two years. Significant improvements in motion, grip strength, and patient satisfaction were observed between six months and one year, but further improvements were not seen at the two-year follow-up examination. The mean DASH score changed from a preinjury baseline of 2 points to 8 points at one year and 7 points at two years (p < 0.0001). The mean Gartland and Werley score improved significantly from 4 points at six months to 2 points at two years. Of the 102 intra-articular fractures examined in the immediate postoperative period, twenty had a step-off of ≤2 mm and seven had a step-off of >2 mm. Of the seventy-one intra-articular fractures seen at two years, sixty-one had no step-off, five had a step-off of ≤2 mm, and five had a step-off of >2 mm. Twenty-seven percent of the patients showed an increase of at least one grade in radiographic signs of arthritis at two years. There were twenty-eight complications, twenty of which were considered minor. Tendon inflammation occurred in nine patients. There were two tendon ruptures, one of which was due to a prominent dorsal screw tip placed through a volar plate and one of which was due to a prominent volar plate. Loss of reduction occurred in two patients, and screw loosening occurred in two patients.Conclusion: Internal fixation of displaced distal radial fractures with implants featuring locking screw fixation can result in good-to-excellent outcomes with a limited number of complications.Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.