Water availability plays a critical role in shaping species distributions, diversity, and ecosystem function in tropical forests. Specifically, there is mounting evidence that drought is a key driver of tropical forest dynamics. Given that the severity and frequency of drought events are predicted to increase due to climate change, there is an urgent need to understand how tropical forests respond to severe drought events. In particular, a better understanding of drought impacts on the regeneration of tree seedlings is critical for determining future tropical forest composition, diversity, and function. The strong 2015-16 El Niño-Southern Oscillation (ENSO) event provided a rare opportunity to study the impact of severe drought on tropical forests. Methods: Across a strong rainfall gradient spanning ~65 km in central Panama, we censused seedlings at eight lowland seasonal forest sites. At each site, we established 400 1x1 m seedling plots in which all freestanding, woody seedlings >=20cm tall and <1cm DBH were tagged, measured, and identified to species. Smaller seedlings (0 - 30 cm tall) were censused in an additional 25 seedling plots per site. The first census was conducted Sept-Dec 2013, with recensuses in Oct-Nov 2014, Jan 2016, May-June 2016, and Jan-Feb 2017. With these data, we compare seedling survival across the El Nino year with survival in the two previous years, as well as between the dry and wet season. Results: We found wide variation in seedling mortality among years, with elevated seedling mortality during the El Nino year compared to the two previous years. Mortality was significantly higher in the dry season compared to the wet season during El Nino year, suggesting that drought played a key role in driving patterns of mortality. In addition, species varied widely in their mortality rates and differed in their sensitivity to drought. Seedling dynamics also varied substantially among sites spanning the rainfall gradient. Discussion/Conclusions: Our results shed light on the fundamental role of water availability in driving tropical forest dynamics, particularly seedling regeneration. Our data on differential effects of drought on species and across forest sites will inform efforts to model responses of tropical forests to extreme drought events, allowing for better predictions of the consequences of global change and improved strategies for forest management in a changing world.