Several important isotopic biomarkers derive at least part of their signal from leaf water stable isotope composition (e.g., leaf wax δ2H, cellulose δ2H and δ18O, lignin δ18O). In order to interpret these isotopic proxies, it is therefore helpful to know which environmental variable most strongly controls leaf water stable isotope enrichment. We collated observations of the stable isotope compositions of leaf water, xylem water, and atmospheric vapour, along with air temperature and relative humidity, to test whether the dominant driver of leaf water 2H enrichment could differ from that for 18O enrichment. Our dataset comprises 620 observations from 39 sites with broad geographical coverage. We limited our analysis to daytime observations, when the photosynthetic processes that incorporate the leaf water isotopic signal into organic material take place. The Craig-Gordon equation was generally a good predictor for daytime leaf water stable isotope composition for both δ2H (R2=0.93, p<0.001) and δ18O (R2=0.70, p<0.001). Solving the Craig-Gordon equation requires knowledge of relative humidity, air temperature, and the stable isotope compositions of xylem water and atmospheric vapour. However, it is not possible to invert the Craig-Gordon equation to solve for one of these parameters unless the others are known. Here we show that the two isotopic signals of 2H and 18O are predominantly driven by different environmental variables: leaf water δ2H correlated most strongly with the δ2H of atmospheric vapour (R2=0.79, p<0.001), whereas leaf water δ18O correlated most strongly with air relative humidity (R2=0.45, p<0.001). We conclude that these two isotopic measures are not simply mirror images in the environmental information that they carry. This has with crucial implications for interpretation of isotopic proxies that derive at least part of their composition from leaf water stable isotopes.Read less <