The main objective of study is to compare the adverse drug reactions (ADRs) of Zidovudine and Stavudine containing regimens.It is a prospective observational study conducted in the ART centre of a tertiary care teaching hospital in central India. The data collected were recorded on standard ADR reporting forms. Standard scales were used for assessment of ADRs.In twelve months duration total 263 patients on ART were observed for ADRs. 128 patients on Stavudine based regimen and 135 patients were on Zidovudine based regimen. Total 72 ADRs detected in 68 patients. Incidence of ADRs was more in Zidovudine based regimen. Zidovudine associated with early and mild ADRs while Stavudine associated with late and distressing ADRs. Considering the magnitude of ADR related problems, results support the discontinuation of Stavudine based regimens.