Water vapor in the tropical tropopause layer (TTL) has a significant radiative cooling effect on the Earth's climate system. As a source for cirrus clouds, however, it can also indirectly produce infrared heating. The amount of water vapor in the TTL is strongly controlled by temperature (correlation <i>r</i>=0.94) with a seasonal cycle of ~1–2 ppm vmr in amplitude at 100 hPa and minimum values in Northern Hemisphere winter (December–January-February, DJF). Studying the A-Train CALIPSO cirrus and MLS water vapor measurements, we find that the cirrus seasonal cycle is highly (<i>r</i>=−0.9) anticorrelated with the water vapor variation in the TTL, showing higher cloud occurrence during DJF. We further investigate the anticorrelation on a regional scale and find that the high anticorrelation occurs generally in the ITCZ (Intertropical Convergence Zone). The seasonal cycle of the cirrus ice water content is also highly anticorrelated to water vapor (<i>r</i>=−0.91) and our results support the hypothesis that the total water is roughly constant in the TTL at 100 hPa. Temperature acts as a main regulator for balancing the partition between water vapor and cirrus clouds. Thus, to a large extent, the depleting water vapor in the TTL during DJF is a manifestation of cirrus formation.