Joint replacements should be firmly anchored in vital bone to avoid early implant subsidence and late aseptic loosening. We investigated whether the fixation of orthopedic implants could be improved by adding an osteoinductive extract of lyophilized equine bone matrix proteins (Colloss E, Ossacur AG, Germany), between the implant and the surrounding bone. Eighteen uncemented HA-coated implants were inserted pairwise in the proximal tibia of nine dogs. All implants were surrounded by a 2 mm concentric defect. In each dog, the intervention implant was added 20 mg protein lyophilisate. The contralateral control implant was inserted untreated. After four weeks, the treated HA-coated implants had better mechanical fixation than the untreated control implants. The treated implants were better osseointegrated, there was more newly formed bone around these implants, and fibrous tissue was eliminated. The mechanical implant fixation had a strong positive correlation to new bone formation on and around the implant, and a strong negative correlation to fibrous tissue encapsulation. The results suggest that bone protein extracts such as the Colloss E device may augment early implant fixation of even HA-coated Ti implants and thereby reduce the risk of long-term failure. This may be particularly useful in revision arthroplasty with bone loss. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.