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The data set represents the Regional Meteoric Water Line (RMWL) for the Yucatan Peninsula (Mexico), a region with karstic aquifers but little knowledge of the isotopic composition of meteoric water. This data paper comprises the isotopic composition of meteoric water collected from November 2018 to November 2019 as monthly composite samples expressed as weighted monthly mean precipitation from 16 locations across the Yucatan Peninsula. The RMWL was δ2H = 7.803 δ18O + 12.075, with a slope and intercept suggesting precipitation from air that has undergone condensation, air masses with variable moisture or recycled moisture. The average δ18O is −2.57‰ (−12.23 to 1.2‰) and δ2H is −7.94‰ (−83.39 to 18.32‰). This data set was collected by the implementation of an isotopic monitoring network, gathering information useful as a tool for better understanding of the hydrology and hydrogeochemistry of karstic aquifers, and to develop proxies for paleohydrology, ecohydrology, climate change and paleoclimate studies in the Gulf of Mexico and the Great Caribbean Area. [ABSTRACT FROM AUTHOR]