Seventy-five patients with ankle osteoarthritis (OA) were randomized to receive either an intraarticular injection of botulinum toxin A (BoNT-A) or an intraarticular injection of hyaluronate with a home-based exercise program. The purpose of this study was to compare the efficacy of these two conservative treatment approaches with respect to clinical and functional outcomes. Results at 6 months indicated that there were no significant differences between groups with respect to Ankle Osteoarthritis Scale (AOS) scores, American Orthopedic Foot and Ankle Society (AOFAS) Ankle/Hindfoot scores, pain, single-leg stance test (SLS) scores, the Timed Up-and-Go test (TUG), patient global satisfaction, acetaminophen consumption, and the incidence of adverse events.