Background: There are two approved non-nucleoside reverse transcriptase inhibitor antiretroviral drugs; namely Nevirapine (NVP) and Efavirenz (EFV). Nevirapine and EFV have comparable clinical efficacy when administered in combination regimens. But there is a lack of recent evidence showing the effect of NVP and EFV-based ARTs on immunological responses in HIV infected individuals in Ethiopia in general and Addis Ababa in particular. Methods: Retrospective cohort study design was used to compare immunological response rate of NVP and EFV based HAART regimen in Addis Ababa. Four hundred ninety two HIV infected patients who started HAART in ten selected health facilities were included in the study. Rate of immunologic response was examined at the 6 th , 12 th , 18 th , and 24 th months of follow-up period. The time required to get immunological response was analyzed by Kaplan-Meier survival curve. Adjusted hazard ratio was calculated with a 95% confidence interval by Cox proportional hazards model to determine the rate of immunological response. To ascertain the association, bivariate and multi variable Cox proportional hazard model was used. Statistical significance was considered with two sides P-value of 0.05. Results: The mean CD4 count ranged between 132.2 cell/µl at baseline and 302.3 cell/µl at the end of the follow-up period. This change was significant at 95% of CI but did not show significant differences among the comparison group. The median time to get immunological response was 18 (75% percental 12) months. At the end of the follow-up period, 73.2% (76.6% for NVP and 69.8% for EVF P-value 0.13) of the study population had immunological response. Conclusion: As a conclusion, there was a robust and sustained CD4 response and the effect of NVP and EFV based ART on change of mean CD4 count and immunological response was comparable and effective. Initiation of ART with high baseline CD4 count, in combination of IPT and with either NVP or EFV based NNTI was recommended.