Objective: To assess the vaccine loss related to the Expanded Program on Immunization (EPI) in Xinjiang Uygur Autonomous Region so as to improve the management of vaccines. Methods: A total of 135 vaccination clinics were randomly selected, using a stratified cluster sampling method. In each clinic, data on vaccination was collected between 2016 and 2017, including the number of doses in routine immunization program and supplementary immunization activities (i.e., vaccine doses in vials that were opened for use) on polio vaccine, number of doses administered to children and the number of doses discarded (e.g., expired vaccine or broken vials that had not been opened for use), etc. Coefficient on vaccine loss was calculated with the following equation: vaccine loss coefficient=(number of vaccine doses used)/(number of vaccine doses administered). The vaccine discard rate appeared as: number of vaccine doses discarded)/number of vaccine doses used. Results: For vaccines in single-dose vials [diphtheria-tetanus-pertussis vaccine (DTaP) and trivalent oral polio virus vaccine (tOPV)], the loss coefficients appeared as 1.00 and 1.02, respectively. For vaccines in multi-dose vials [bivalent oral polio vaccine (bOPV), group A meningococcal polysaccharide vaccine (MPV-A), diphtheria-tetanus combined vaccine (DT) and bacilli Calmette-Guérin (BCG) vaccine], the loss coefficients were 1.58, 1.67, 1.68, and 3.02, respectively. The coefficients of EPI vaccine loss in urban, rural, and pastoral area vaccination clinics ranged between 1.00-2.84, 1.00-3.71, and 1.00-2.27, respectively. Loss coefficients ranged between 1.00-3.00, 1.00- 4.41, and 1.00-1.94, respectively, were seen in township clinics, village clinics, and decentralized vaccination clinics. Coefficients on larger vaccine loss were associated with longer intervals between clinic sessions and with fewer vaccinations administrations per day. Conclusions: In Xinjiang, coefficients on the loss of multi-dose EPI vaccines were high. The coefficients on loss were different from the levels of region and types of clinics, and time interval between clinic sessions. Programs on refining the management and distribution of EPI vaccines, to minimize the vaccine loss were recommended.