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The Aetiology of Neonatal Infection in South Asia (ANISA) study aims to determine the population-based incidence, etiology, risk factors and antibiotic resistance profiles of community-acquired young infant infections in Bangladesh, India and Pakistan using community-based surveillance and standard newer diagnostic tests. The data generated will help plan preventive and treatment strategies to reduce neonatal and infant mortality in this region. The aim of this article is to describe the site-specific characteristics, challenges and solutions in implementing the ANISA protocol at the Vellore site, India.Vellore joined the ANISA study 2 years after the sites in Bangladesh and Pakistan, and some challenges relate to the need for rapid implementation. The Vellore site differs primarily in the high rate of institutional deliveries, actively promoted by the Government of India’s conditional cash transfer program. The Vellore site hospitals are regular care providers for the study population, which leads to very high rates of consent for enrollment and collection of samples. Keeping blood culture contamination rates low was a challenge the site team overcame by adhering strictly to the protocol. Issues related to incorporation of a large study into a busy clinical services laboratory were overcome by meticulously setting up algorithms related to receipt, processing and storage of samples.ANISA is a complex study, but the challenges in implementation have been largely resolved and documented.