HIV-1 treatment-failure patients are increasingly being initiated on second-line antiretroviral therapy. The case we describe is of a treatment-failure patient who developed intractable chronic vulval ulceration presenting as immune reconstitution inflammatory syndrome (IRIS), following complete viral suppression with second-line highly active antiretroviral treatment (HAART). To the best of our knowledge, this is the first reported case of intractable vulval ulceration IRIS in an HIV-1 treatment-failure patient.