To achieve immunization goals, two factors are necessary; the delivery of potent vaccines to children through properly maintained cold chain systems and achieving high vaccine coverage. Maintaining quality of vaccines has been one of the main challenges of immunization programs in Ethiopia. The Objective of this study is to Assess Factor affecting Vaccine Cold Chain Management Practice in Immunization Health institutions in East Gojjam zone of Amhara region, Ethiopia. An institution based cross-sectional study was conducted in March and April 2017 in ten districts of East Gojam zone of Amhara Region, data was collected from 60 health institutions. Multiple logistic regression analysis was carried out to identify factors related to practice of cold chain management. Of visited 60 health institutions only 46(76.7%) were functional. Twenty one (35%) had a functional generator for backup service and 28(46.6%) had a car/motorbike for transportation of vaccines in case of refrigerator/power failure. Of 60 respondents 58(96.7%) had known that vaccines are heat sensitive drugs. Twenty nine (48.3%) had known the correct vaccine storage temperature (20C - 80C) in refrigerator the results of this study revealed that only 23(38.3%) of respondents has sufficient knowledge about vaccine cold chain management. The finding of this study revealed that 35(58.3%) has good Vaccine cold chain management practice the rest 25(41.7%) has inappropriate practice. Professional qualification and aver all knowledge on cold chain management showed a statistically significant association with practice of cold chain management (P < 0.05). This study indicates that there are knowledge gaps of health workers who are working on cold chain management. Vaccine cold chain management has significantly associated with the overall cold chain management knowledge and profession of health care worker in health institutions. There is an urgent need to improve knowledge and practice on cold chain management through improved supervision and training at different level of health care system.