Background: Elimination of MTCT of HIV was a global public health priority. In 2013, the World Health Organization recommended antiretroviral therapy administration to all HIV positive pregnant, and breastfeeding women regardless of CD4 cell count or clinical stage, which is called “Option B+”. Ethiopia have had a high rate of MTCT of HIV. The rate of transmission on breastfeeding mothers was 24% in 2012. But the rate had been increased to more than 30% in 2015.Objective: This study aimed to determine outcomes of HIV exposed infants, explore the contributors of mortality and loss to follow up, and identify factors of HIV transmission among infants born from HIV positive mothers in Amhara regional state referral hospitals, Ethiopia, 2018/19. Methods: The study was done in five Amhara regional state referral hospitals’ PMTCT departments. A simple random sampling technique with proportional allocation was used to assess the outcomes of 217 exposed infants. A retrospective quantitative cohort design and qualitative exploratory design were used in all referral hospitals of the Amhara region. The data were collected from each hospital exposed infant medical record, which was documented between January 01/2014 and May 30/2017 . An in-depth interview was also taken place from health professionals working in the PMTCT department, zonal HIV officers, and mothers who are enrolled in the PMTCT department. A cumulative incidence rate was used to present mortality, transmission, and loss to follow- up.Results: The incidence rate of HIV transmission at enrollment to PMTCT program in Amhara regional state referral hospitals was 2.3% (95% CI, 0.5-4.6%), and 3.7 (95% CI, 1.4-6.5) at the time of completing PMTCT program using antibody or DNA-PCR test. Whereas the incidence rate of LTFU in Amhara regional state referral hospitals was 8.8% (95% CI, 5.4-12.4%). But the rate of mortality after enrollment to the program was zero. The interviewees’ opinions on mortality, and loss to follow up were categorized into themes.Conclusions: Irrespective of the WHO guideline expected outcome of option B+, the outcome of the PMTCT program in this study was high, particularly HIV transmission and LTFU.