Using data from TREAT Asia HIV Observational Database (TAHOD), this paper aims to assess the rate of, and factors associated with the diagnosis of new AIDS-defining illness (ADI) within 90 days after antiretroviral treatment. Patients starting three or more antiretroviral combinations and having subsequent follow-up were included. New ADI cases were checked for evidence of immune reconstitution syndrome (IRS). Among the 1185 patients included, 75 (6.3%) were diagnosed with a new ADI within 90 days, giving a rate of 26.8/100 person-years, compared with a further 3.6% cumulative incidence of new ADI between 90 days to one year (4.2/100 person-years). Of the 75 patients, 21 were judged as definitive or presumptive IRS, giving a rate of 7.3/100 person-years. Patients with new ADI generally had lower CD4 counts before treatment started (median, 43 cells/microL). Lower CD4 count, lower body mass index and starting treatment in the same year as the first HIV-positive test done were associated with developing a new ADI. The higher rate of new ADI within 90 days may be partly explained by IRS occurring shortly after treatment. Although it is difficult to identify IRS from observational data, it appears that in TAHOD setting IRS was relatively uncommon.