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It has been suggested that, when a patient has a giant cell tumor, subchondral bone involvement close to articular cartilage and a hyperthermic reaction from polymethylmethacrylate (PMMA) are risk factors for the development of osteoarthritis. We determined the prevalence, risk factors, and clinical relevance of osteoarthritis on radiographs after curettage and application of PMMA for the treatment of giant cell tumors around the knee.This retrospective single-center study included fifty-three patients with giant cell tumor around the knee treated with curettage and PMMA between 1987 and 2007. The median age at the time of follow-up was forty-two years (range, twenty-three to seventy years). There were twenty-nine women. Radiographic evidence of osteoarthritis was defined, preoperatively and postoperatively, as Kellgren and Lawrence grade 3 or 4 (KL3-4). We studied the influence of age, sex, tumor-cartilage distance, subchondral bone involvement (≤3 mm of residual subchondral bone), subchondral bone-grafting, intra-articular fracture, multiple curettage procedures, and complications on progression to KL3-4. Functional outcomes and quality of life were assessed with the Short Form-36 (SF-36), Musculoskeletal Tumor Society (MSTS) score, and Knee injury and Osteoarthritis Outcome Score (KOOS).After a median duration of follow-up of eighty-six months (range, sixty to 285 months), six patients (11%) had progression to KL3, two (4%) had progression to KL4, and one had preexistent KL4. No patient underwent total knee replacement. The hazard ratio for KL3-4 was 9.0 (95% confidence interval [CI] = 2.0 to 41; p = 0.004) when >70% of the subchondral bone was affected and 4.2 (95% CI = 0.84 to 21; p = 0.081) when the tumor-cartilage distance was ≤3 mm. Age, sex, subchondral bone-grafting, intra-articular fracture, multiple curettage procedures, and complications did not affect progression to KL3-4. Patients with KL3-4 reported lower scores on the KOOS symptom subscale (58 versus 82; p = 0.01), but their scores on the other KOOS subscales, the MSTS score (21 versus 24), and the SF-36 (76 versus 81) were similar to those for the patients with KL0, 1, or 2 (KL0-2).Seventeen percent of patients with giant cell tumor around the knee had radiographic findings of osteoarthritis after treatment with curettage and PMMA. A large amount of subchondral bone involvement close to articular cartilage increased the risk for osteoarthritis. The function and quality of life of the patients with KL3-4 were comparable with those for the patients with KL0-2, suggesting that radiographic findings of osteoarthritis at the time of intermediate follow-up had a modest clinical impact. Treatment with curettage and PMMA is safe for primary and recurrent giant cell tumors, even large tumors close to the joint.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.