Immune reconstitution inflammatory syndrome (IRIS) occurs as an acute symptomatic expression of a latent infection during the recovery of immune system in response to antiretroviral therapy in HIV patients. IRIS triggers both opportunistic and non-opportunistic infections. We report a case of IRIS in a patient with HIV, presenting as erythema nodosum leprosum (ENL), which led to unmasking of lepromatous leprosy following anti-retroviral therapy (ART).