Carbonate cave deposits (speleothems) have been used widely for paleoclimate reconstructions; however, few studies have examined the utility of other speleothem-forming minerals for this purpose. Here we demonstrate for the first time that stable isotopes (delta O-17, delta O-18 and delta D) of structurally-bound gypsum (CaSO(4)2H(2)O) hydration water (GHW) can be used to infer paleoclimate. Specifically, we used a 63 cm-long gypsum stalactite from Sima Blanca Cave to reconstruct the climate history of SE Spain from similar to 800 BCE to similar to 800 CE. The gypsum stalactite indicates wet conditions in the cave and humid climate from similar to 200 BCE to 100 CE, at the time of the Roman Empire apogee in Hispania. From similar to 100 CE to similar to 600 CE, evaporation in the cave increased in response to regional aridification that peaked at similar to 500-600 CE, roughly coinciding with the transition between the Iberian Roman Humid Period and the Migration Period. Our record agrees with most Mediterranean and Iberian paleoclimate archives, demonstrating that stable isotopes of GHW in subaerial gypsum speleothems are a useful tool for paleoclimate reconstructions.