Intravenous regional perfusion is a common technique for treating infections of the extremities in humans and horses. It has the advantage of achieving very high antibiotic concentrations in affected tissues. This technique was used to clinically resolve deep, mixed infections involving bones and joints in a swamp wallaby and a lesser kudu. Both infections were severe and considered life-threatening, because amputation was not feasible, systemic antibiotic treatment had failed, and both animals were in pain and had evidence of the systemic effects of the infections. In the wallaby, once daily treatments with imipenem for 5 days resulted in a return to normal function within 1 mo. In the kudu, four treatments using both ampicillin/sulbactam followed by enrofloxacin were performed every 2 days, followed by two treatments with ampicillin/sulbactam alone 2 wk later. Resolution of this case was achieved in less than 2 mo. The only adverse effect noted was phlebitis in the kudu, which resolved with conservative therapy. Healing was rapid in both cases and was apparent after two treatments. This report demonstrates the efficacy and flexibility of intravenous regional perfusion for the treatment of severe infections of the digits in nondomestic species.