A 2-year-old female American white pekin (Anas platyrhynchos domesticus) was assessed for a 2-month history of chronic lameness and swelling involving the left leg. Radiographic images of the left leg showed soft tissue swelling of the digits and tarsometatarsus with osteolysis of the tarsometatarsal-phalangeal joint. A complete blood count revealed marked leukocytosis and hyperproteinemia. A Streptococcus species was isolated from a bacterial culture of fluid obtained from the left tarsometatarsal-phalangeal joint. Biweekly intravenous regional limb perfusions of the left leg with ampicillin-sulbactam and amikacin were performed on the patient. Despite initial improvement in left leg lameness and swelling, follow-up radiographic images showed progressive osteolysis of the tarsometatarsal-phalangeal joint and associated digits. Surgical placement of antibiotic-impregnated calcium sulfate beads into the left tarsometatarsal-phalangeal joint was next performed with concurrent, repeated intravenous regional limb perfusion using the same antibiotic. Following the placement of antibiotic-impregnated beads and continued intravenous regional limb perfusion, the duck had decreased lameness and swelling of the left leg. Repeated antibiotic treatment through intravenous regional limb perfusion and concurrent placement of antibiotic-impregnated calcium sulfate beads is a practical treatment option for complicated distal limb infections in avian species. This therapeutic protocol has great potential in treating aggressive distal leg infections in many avian species because regional limb perfusion alone may not penetrate the joint adequately to achieve complete resolution of infection.