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• One-dose UVV introduction in 2015 significantly reduced clinical burden of varicella in Colombia. • This study showed a direct benefit of UVV in children aged 1–4 years of age (target population). • We also observed indirect benefits of herd immunity in the overall population. • Long-term follow up is needed to understand the full impact on varicella-related mortality. In 2015, one-dose universal varicella vaccination (UVV) was introduced in the Colombian National Immunization Program targeting children aged 12 months, expanding to a two-dose program in 2019. This study aimed to examine the effect of one-dose UVV on the burden of varicella in Colombia. A retrospective study was conducted using national databases to estimate incidence and mortality for the target (1–4 years old), non-target (less than 1 and 5 years and older) and overall (all age groups) populations from the pre-UVV period (January 2008–June 2015) to the post-UVV period (July 2015-December 2019). A time-series analyses with ARIMA modeling was used to project expected varicella incidence and mortality in the absence of UVV in the post-UVV period. UVV impact was estimated by comparing predicted and observed values, providing point estimates and prediction intervals (PI). Overall vaccination coverage rate was over 90 % from 2016-2019. Following UVV introduction, mean annual incidence rates reduced from 743.6 to 676.8 per 100,000 in the target population and from 203.2 to 198.1 per 100,000 in the overall population. Our study estimated a reduction in varicella incidence from 2017, with the highest reduction of 70.5 % (95 % PI: 78.2-54.2) and 54.8 % (95 % PI: 65.0-36.4) observed in 2019 for the target and the overall populations, respectively. The ARIMA model estimated UVV in Colombia to have prevented 198,236 varicella cases from 2015 to 2019. Mortality reduced in the overall population from 0.8 per 1,000,000 to 0.5 per 1,000,000 and from 1.3 per 1,000,000 to 0.5 per 1,000,000 in the target population, in the pre-UVV and post-UVV periods, respectively. However, these differences were not statistically significant. Our study showed a significant reduction in varicella incidence after implementation of a one-dose UVV program in Colombia, increasing over time. Further assessment is needed to evaluate the impact of a two-dose UVV program in Colombia. [ABSTRACT FROM AUTHOR]