Mid-Cretaceous δ18O paleotemperatures are compared with temperatures predicted by an ocean general circulation model. The δ18O paleotemperatures, calculated assuming a δw of −1.0‰ (SMOW), are 5.6°C lower at low latitudes and 2.4°C higher at middle and high latitudes than the model-predicted, mixed-layer temperatures. The model-data comparison is improved after accounting for the spatial variability of δw and after considering the paleohabitats of the marine organisms from which δ18O values were measured. Paleotemperatures adjusted using the Broecker  δw-S relationship and the model-predicted salinity are 3.4°C higher at low-latitude sites and 1.9°C lower at higher-latitude sites. Moreover, seven of nine low-latitude paleotemperatures intersect the model-predicted temperature within the upper 100 m of the water column, a depth consistent with the interpreted paleohabitat of the analyzed organisms. However, adjusted paleotemperatures for three of five Southern Hemisphere high-latitude locations are at least 9°C higher than the model-predicted temperatures for these locations. The model-data comparison suggests that mid-Cretaceous δ18O values are compatible with sea surface temperatures as high or higher than those simulated by an ocean general circulation model of the mid-Cretaceous with 4 × present-day atmospheric pCO2.