Background: Immunization is one of the most cost effective and efficient interventions saving the lives of many millions of infants and children preventing childhood morbidity, mortality, and disability from infectious and preventable diseases .However children in Africa was not fully immunized with in the recommended vaccines. Thus many children are still susceptible to the expanded program on immunization target disease. Data from world health organization (2018), 20 million children miss out on lifesaving vaccines such as measles, diphtheria and tetanus and 2–3 million children are dying annually from easily preventable diseases and many more fall ill. The study aimed to identify determinant factors of dropout from vaccination among children age 15-23 month in Gonji-kollela district, North West Ethiopia 2021. Methods: Community based unmatched case control study was conducted from September1-30 2021 and total of 225(75cases, 150controls) simple random and systematic sampling technique were used to reach study participants; mothers/caregivers who have children 15-23 month of age were included in the study. The data was collected house to house by using interviewer administered, structured, and a pre-tested questionnaire; and entered, coded, cleaned with epiinfo version 7.3 exported and analyzed using SPSS version 23.0. On multivariable logistic regression variables with P-value <0.05 at 95% CI were considered statistically significant. Result: Counseling mothers about vaccination (AOR = 3.3, 95% CI: (1.19-8.92)); fear of vaccine side effects (AOR = 5, 95% CI: (.043-.489)), primary care giver knowledge on vaccination (AOR= 8, 95% CI: (2.16-29.65)) and distance to reach health facility greater than half hour (AOR = 4.1, 95% CI: (1.1-15.2)) were found determinant of vaccination dropout. Conclusion: Counseling on vaccination, fear of vaccine side effects, primary care provider vaccination knowledge, and a distance to a health facility of more than half hour were all found to be determinants of vaccination dropout; so district health office adds new vaccine sites and strength outreach services; health professional should counsel every mother at every opportunity and deliver vital vaccine message to assist reduce immunization dropout among children. Key words; immunization, dropout, determinant & children