Based on a 6-year long record (2014–2020) of the isotopic composition of rain (δ18Op) at Réunion Island (55°E, 22°S), in the South-West Indian Ocean, this study shows that the annual isotopic composition of precipitation in this region is strongly controlled by the number of cyclones, the number of best-track days, and the proportion of cyclonic rain during the year. Our results support the use of δ18Op in annual-resolved tropical climate archives as a reliable proxy of past cyclone frequency. The influence of the proportion of cyclonic rain on the annual isotopic composition arises from the systematically more depleted precipitation and water vapor during cyclonic events than during less organized convective systems. The analysis of the daily to hourly isotopic composition of water vapor (δ18Ov) during low-pressure systems and the reproduction of daily δ18Ov observations by AGCMs with a global medium to coarse resolution (LMDZ-iso and ECHAM6-wiso) suggest that during cyclonic periods the stronger depletion mainly arises from both enhanced large-scale precipitation and water vapor-rain interactions under humid conditions.