The burden of disease due to influenza is not well characterized for children in developing countries and the effectiveness of available influenza vaccines in lower resource settings has not been established. We initiated a prospective, longitudinal, phase IV, household-randomized, controlled, observer-blinded three year study (2009-2011) in a rural community of India to measure the total and indirect household protective effects of immunizing children ages 6 months through 10 years with seasonal inactivated trivalent influenza vaccine (TIV) or a control vaccine (n=3697). Active weekly surveillance was conducted year round with home visits for identification of febrile acute respiratory illness (FARI) conducted for all vaccine recipients and household members (n=18,220). Nasal and throat swabs were collected from each FARI episode for influenza detection by real-time reverse transcription polymerase chain reaction. The primary outcome was reduction in laboratory confirmed influenza infections in the influenza vaccine versus control vaccine group, with secondary outcome assessing indirect effects among the entire study population. This report describes the study site, cluster study design, choice of study and control vaccines, and the initial enrollment in the study.