There are limited studies on COVID vaccine confidence at the household level in urban slums, which are at high risk of COVID-19 transmission due to overcrowding and poor living conditions. The objective was to understand the reasons influencing COVID-19 vaccine confidence, in terms of barriers and enablers faced by communities in urban slums and informal settlements in four major metro cities in India. A mixed method approach was adopted, where in field studies were conducted during April–May 2021. First, a survey of at least 50 subjects was conducted among residents of informal urban settlements who had not taken any dose of the COVID-19 vaccine in Mumbai, Bengaluru, Kolkata and Delhi; second, a short interview with five subjects who had taken at least one dose of the vaccine in each of the four cities to understand the factors that contributed to positive behaviour and, finally, an in-depth interview of at least 3 key informants in each city to ascertain the vaccination pattern in the communities. The reasons were grouped under contextual, individual/group and vaccine/vaccination specific issues. The most frequent reason (27.7%) was the uncertainty of getting the vaccine. The findings show the need for increasing effectiveness of awareness campaigns, accessibility and the convenience of vaccination, especially among vulnerable groups, to increase the uptake.