The World Health Organization (WHO) in 2008 recommended the use of currently licensed typhoid vaccines using a high risk or targeted approach. The epidemiology of disease and the vaccine characteristics make school-based vaccination most feasible in reducing typhoid disease burden in many settings. To assess feasibility of school-based typhoid vaccination, two districts in Kathmandu, Nepal and two towns in Karachi, Pakistan were selected for pilot program. Vaccination campaigns were conducted through the departments of health and in partnerships with not-for-profit organizations. In total 257,015 doses of Vi polysaccharide vaccine were given to students in grades 1–10 of participating schools. The vaccination coverage ranged from 39 percent (38,389/99,503) in Gulshan town in Karachi, to 81 percent (62,615/77,341) in Bhaktapur in Kathmandu valley. No serious adverse event was reported post vaccination. The coverage increased for vaccination of the second district in Pakistan as well as in Nepal. There was an initial concern of vaccine safety. However, as the campaign progressed, parents were more comfortable with vaccinating their children in schools. Supported and conducted by departments of health in Pakistan and Nepal, a school-based typhoid vaccination was found to be safe and feasible.