Objective: Demonstrate if the introduction of more and more efficacious antiretroviral (ARV) combinations for prevention of mother-to-child transmission (PMTCT) over time translated into a declining HIV-infection among HIV-exposed infants. Methods: This was a retrospective review of routinely collected PMTCT service data from 2008 to 2014 in 682 secondary and tertiary health facilities across Nigeria. The ARV regimen was measured by the proportions of different ARV regimens received by HIV-positive pregnant women each year and the HIV-infection among infants was determined by the rate of HIV-positive polymerase chain reaction tests each year. The District Health Information Software (DHIS) was used to extract data from health facilities. The same DHIS was used to aggregate and analyze data. Results: Maternal HIV positivity rates varied from 4.1% in 2008, 2.9% in 2011, and 3.2% in 2012, then declined steadily to 1.9% in 2014. The total number of pregnant women who tested positive for HIV and received different ARV regimen for PMTCT during the period (2008-2014) was 63,774; ranging from 7506 in 2008 to 10,388 in 2014. Uptake of single dose nevirapine by the positive pregnant women was 34.4%, 41.6%, and 45.9% in 2008, 2009, and 2010, respectively. HIV positive pregnant women on triple ARVs (prophylaxis or treatment) increased from 22% in 2008 to 99% in 2014. Infant HIV positivity rates showed a steady decline over the years, from 38% in 2008 to 6% in 2014 (P < 0.001). Conclusions: We demonstrated the declining trend of HIV-infection among HIV-exposed infant in Nigeria as more and more efficacious ARV regimens were available for HIV-positive pregnant women. We conclude that if current efforts were sustained and coverage widened, an alignment of the country's PMTCT program with the best available scientific evidence could lead to the elimination of mother to child transmission.