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Background Varicella causes a major health burden in many low- to middle-income countries located in tropical regions. Because of the lack of surveillance data, however, the epidemiology of varicella in these regions remains uncharacterized. In this study, based on an extensive dataset of weekly varicella incidence in children ≤10 during 2011–2014 in 25 municipalities, we aimed to delineate the seasonality of varicella across the diverse tropical climates of Colombia. Methods We used generalized additive models to estimate varicella seasonality, and we used clustering and matrix correlation methods to assess its correlation with climate. Furthermore, we developed a mathematical model to examine whether including the effect of climate on varicella transmission could reproduce the observed spatiotemporal patterns. Results Varicella seasonality was markedly bimodal, with latitudinal changes in the peaks' timing and amplitude. This spatial gradient strongly correlated with specific humidity (Mantel statistic = 0.412, P =.001) but not temperature (Mantel statistic = 0.077, P =.225). The mathematical model reproduced the observed patterns not only in Colombia but also México, and it predicted a latitudinal gradient in Central America. Conclusions These results demonstrate large variability in varicella seasonality across Colombia and suggest that spatiotemporal humidity fluctuations can explain the calendar of varicella epidemics in Colombia, México, and potentially in Central America. [ABSTRACT FROM AUTHOR]