Objective: Comparative study of the adverse effects of antiretroviral drug regimen ZLN and TLE as first line ART in the initial 3 months of starting of therapy in 300 patients in MBGH,Udaipur, Rajasthan. Methods: This was a retrospective observational study. Patient’s records were obtained from ART Centre, MBGH Udaipur from starting of HAART to 3 months of treatment for clinical and laboratory evidence of toxicity as per NACO protocol. Results: Total 300 patients were observed. Most common side effect was anemia mostly associated with Zidovudine based regimens followed by drug hypersensitivity and hepatotoxicity which was with nevirapine based regimen. Least was neuropsychiatric side effects which was with Tenofovir and Efavirenz based regimen. Drug hypersensitivity seems to be the most serious of the early toxicities & is the most common causes for interruption in ART. Conclusion: With introduction of new NACO guidelines in November 2014, TLE regimen was chosen over ZLN in all new HIV patients. The reason for such an important step taken by NACO can be easily understood by the results and observation of this study as TLE regimen is superior to ZLN regimen.