OBJECTIVES: No multicenter studies currently assess the incremental costs of autogenous bone graft harvest (autograft) in foot and ankle procedures. This study applied conservatively estimated incremental costs of autograft (with and without bone graft supplements/enhancers) using an interactive budgetary impact model comparing costs and cost offsets of an orthobiologic bone graft substitute (β-TCP with recombinant human platelet-derived growth factor-BB [rhPDGF-BB]) in foot and ankle fusion procedures. METHODS: A Canadian hospital-based budget impact model was developed utilizing International Society of Pharmacoeconomics and Outcomes Research (ISPOR) guidelines.  Clinical and health economic literature, data from a 434-patient randomized control trial and data from a panel of ten experienced orthopaedic surgeons provided estimates of medical resource utilization and associated hospital costs.  Model parameters were confirmed by six individuals representing 15 Canadian hospitals. RESULTS: Autograft carries incremental costs related to operating suite time (37.9 ± 17.0 minutes for an iliac crest donor site and 22.1 ± 21.6 minutes for local donor sites), recovery room time (25.0 ± 12.3 minutes for iliac and 3.5 ± 9.4 minutes for local), and donor site complications. Conservative base case incremental costs were $1,601(CAD) for iliac crest and $755 (CAD) for local sites. Complications at the harvest site contributed an additional base case cost of $414 for iliac crest and $182 for local sites. Use of an orthobiologic bone graft substitute had higher acquisition costs, but yielded per-case and annualized cost savings ($34 and $2,454, respectively, base case) by eliminating incremental costs, graft harvest complications, and patient pain reported for autograft harvest during clinical trial. CONCLUSIONS:  The gold standard of harvesting autogenous bone graft as an adjunct to foot and ankle fusion surgery is associated with significant healthcare costs.  The use of β-TCP with rhPDGF-BB eliminated variable, incremental hospital costs associated with bone graft harvesting and treating related complications.