Pakistan ranks third globally in the number of unvaccinated and under-vaccinated children, and Sindh province has one of the lowest vaccination rates in the country. Electronic census-based immunization information systems have the potential to bolster traditional immunization service delivery mechanisms, but literature has largely not focused on implementation at scale in Pakistan. This is a case report of technical support provided to the Sindh Department of Health/Expanded Program on Immunization (DOH/EPI) from 2015 to 2017 to strengthen routine immunization (RI). The program developed an immunization information system used by district health officers to register and track individual immunization status, improve vaccine logistics, and generate more accurate population estimates and vaccination targets. District immunization officers (DIOs) assisted their district health management teams and supervisors to use registration and service data stored in the immunization information system database to prepare microplans, monitor catchment area performance, and solve problems. Civil society partners registered 830,610 children (aged 0 to 23 months) and 348,315 pregnant women in 28,565 villages over an 18-month intensive intervention period. By the end of this period, 65% of all registered women had been vaccinated with two or more doses of the tetanus toxoid vaccine (compared to 26% at baseline); Penta 3 vaccination coverage had increased from 27% to 64%; and 52% of the registered children (aged 0 to 23 months) were fully immunized (compared to 18% at baseline). The immunization information system helped district managers identify and focus limited resources on high-risk populations; reminded families and health providers when vaccinations were due or missed; assisted managers in monitoring vaccination coverage, vaccinator performance, and vaccine stocks; and encouraged local problem solving to improve RI performance. The Government of Sindh demonstrated a commitment to RI based on the program’s results, which bode well to future enhancements and scale up.2020 mHealth. All rights reserved.