Background: Recently, the National Aids Control Organisation (NACO) in India advocated and recommended the use of tenofovir, lamivudine and efavirenz as a fixed-dose combination in initiating ART in all future treatment-naïve patients. The present study was thus undertaken to assess the nature and extent of safety concerns with this regime.Methods: A prospective observational study was carried out in the outpatient setting of nodal ART centre of Eastern India. A total of 242 patients on various ART regimens were studied for suspected ADRs over one year. Adverse event history, medication history and other relevant details were captured. Causality and severity of each reported ADR were duly assessed.Results: Out of 242 PLHIV put on this regimen, 75 patients did not encounter any adverse reactions during the entire study period. Out of remaining 167 patients who presented with a total of 451 ADRs, maximum ADRs were attributed to various psychiatric disorders which included insomnia, dizziness, drowsiness etc, which were followed by gastrointestinal disorders including anorexia, flatulence, nausea, vomiting etc. Dermatological complications included rashes, itching, SJS, pigmentation of nails, skin hyper pigmentation respectively.Conclusions: The study enables to obtain information on the pattern of adverse drug reactions associated with treatment naïve PLHIV put on first line antiretroviral regimen comprising of once daily dosing of tenofovir, lamivudine, efavirenz. Need of intensive monitoring for ADRs in ARTs followed with proper patient counselling regarding its nature can lead to better compliance to the therapy.