Refractory gout can be treated with infusions of pegloticase, which metabolizes uric acid into a product readily excreted in urine. Antidrug antibodies often develop, leading to reduced efficacy and potential infusion reactions. The concomitant administration of immunosuppressive agents has been suggested as a means of mitigating the effects of drug-related immunogenicity, rendering treatment more tolerable, and resulting in better outcomes. This report presents cases of 2 patients with tophaceous gout, each having previously undergone a solid-organ transplant, each taking immunosuppressants to prevent organ rejection, and each successfully treated with pegloticase. Although data from randomized controlled studies are needed, these cases suggest that it may be beneficial to coadminister an immunosuppressive medication to extend drug persistence with pegloticase in the management of refractory gout. This approach could allow patients to receive long-term treatment, resulting in improved patient outcomes.