['Autologous chondrocyte implantation is associated with a high rate of reoperation, mostly due to hypertrophy of the periosteal patch. European studies investigating the use of collagen membranes as a periosteal substitute report significant decreases in reoperation rates to less than 5%. This multicenter study investigates the off-label use of 1 collagen membrane as a periosteal substitute for autologous chondrocyte implantation.', 'The use of a collagen membrane for autologous chondrocyte implantation will decrease reoperation rates for hypertrophy with comparable rates of failure.', 'Cohort study; Level of evidence, 3.', 'A multicenter cohort of 300 patients treated with periosteal-covered autologous chondrocyte implantation was compared with a consecutive series of 101 patients who underwent collagen membrane-covered autologous chondrocyte implantation with the Bio-Gide membrane by the same group of surgeons. The 1-year hypertrophy-related reoperation rates and overall failure rates of autologous chondrocyte implantation were evaluated in both groups.', 'Both groups were comparable for age (periosteal autologous chondrocyte implantation, 31.9 years; collagen autologous chondrocyte implantation, 32.4 years; P = .8) and average defect size (4.6 cm(2) and 4.7 cm(2), respectively; P = .7). The average number of defects (1.5 and 1.8; P = .001) and total defect area per knee (6.7 cm(2) and 8.6 cm(2); P = .003) were larger in the collagen membrane group. Within 1 year of surgery, 25.7% of patients treated with periosteal-covered autologous chondrocyte implantation required reoperation for hypertrophy and 2.3% were considered to have failed their treatment with autologous chondrocyte implantation. In comparison, only 5% of patients required reoperation for hypertrophy after collagen membrane-covered autologous chondrocyte implantation, and 4% were considered treatment failures.'] Does use of a type I/III bilayer collagen membrane decrease reoperation rates for symptomatic hypertrophy after autologous chondrocyte implantation?