Bone graft augmentation is often selected to treat defects associated with unstable tibial plateau fractures. This prospective, randomized, multicenter study was undertaken to determine the efficacy of bioresorbable calcium phosphate cement compared with standard autogenous iliac bone graft in the treatment of these osseous defects. One hundred and twenty acute, closed, unstable tibial plateau fractures (Schatzker types I through VI) in 119 adult patients were prospectively enrolled in twelve study sites in North America between 1999 and 2002. Randomization for the type of grafting of the subarticular defect was done at the time of surgery, with use of a 2:1 ratio, to treatment with calcium phosphate cement (eighty-two fractures) or autogenous iliac bone graft (thirty-eight fractures). After open reduction, standard plate-and-screw or screw-only fixation was used and then either the cement or the bone graft was placed in the defect cavity for subarticular support. Follow-up included standard radiographs, evaluated by multiple reviewers to avoid bias, and knee range-of-motion assessment at six months to one year or later. The age, weight, height, and sex of the patients and the fracture patterns were comparable in the two groups, as were union rates and time to union. There was a significantly (p = 0.009) higher rate of articular subsidence during the three to twelve-month follow-up period in the bone graft group. The bioresorbable calcium phosphate cement used in this study appears to be a better choice, at least in terms of the prevention of subsidence, than autogenous iliac bone graft for the treatment of subarticular defects associated with unstable tibial plateau fractures. Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.