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Abstract Background This study analyses vaccine coverage and equity among children under five years of age in Uganda based on the 2016 Uganda Demographic and Health Survey (UDHS) dataset. Understanding equity in vaccine access and the determinants is crucial for the redress of emerging as well as persistent inequities. Methods Applied to the UDHS for 2000, 2006, 2011, and 2016, the Vaccine Economics Research for Sustainability and Equity (VERSE) Equity Toolkit provides a multivariate assessment of immunization coverage and equity by (1) ranking the sample population with a composite direct unfairness index, (2) generating quantitative measure of efficiency (coverage) and equity, and (3) decomposing inequity into its contributing factors. The direct unfairness ranking variable is the predicted vaccination coverage from a logistic model based upon fair and unfair sources of variation in vaccination coverage. Our fair source of variation is defined as the child’s age – children too young to receive routine immunization are not expected to be vaccinated. Unfair sources of variation are the child’s region of residence, and whether they live in an urban or rural area, the mother’s education level, the household’s socioeconomic status, the child’s sex, and their insurance coverage status. For each unfair source of variation, we identify a “more privileged” situation. Results The coverage and equity of the Diphtheria-Pertussis-Tetanus vaccine, 3rd dose (DPT3) and the Measles-Containing Vaccine, 1st dose (MCV1) – two vaccines indicative of the health system’s performance – improved significantly since 2000, from 49.7% to 76.8% and 67.8% to 82.7%, respectively, and there are fewer zero-dose children: from 8.4% to 2.2%. Improvements in retaining children in the program so that they complete the immunization schedule are more modest (from 38.1% to 40.8%). Progress in coverage was pro-poor, with concentration indices (wealth only) moving from 0.127 (DPT3) and 0.123 (MCV1) in 2000 to -0.042 and -0.029 in 2016. Gains in overall equity (composite) were more modest, albeit significant for most vaccines except for MCV1: concentration indices of 0.150 (DPT3) and 0.087 (MCV1) in 2000 and 0.054 and 0.055 in 2016. The influence of the region and settings (urban/rural) of residence significantly decreased since 2000. Conclusion The past two decades have seen significant improvements in vaccine coverage and equity, thanks to the efforts to strengthen routine immunization and ongoing supplemental immunization activities such as the Family Health Days. While maintaining the regular provision of vaccines to all regions, efforts should be made to alleviate the impact of low maternal education and literacy on vaccination uptake.