Hydrates are known to affect the solubility of compounds to a larger extent compared to polymorphic forms and thus, exposure. In addition, hydrates are more likely to form during most pharmaceutical processes. Therefore discovery of the propensity of compounds to form hydrates at an early stage allows for adequate precautions and sometimes, selection of compounds. A medium-throughput screen using the Crystal 16™ with an accelerated thermal cycle in a mixed solvent system was developed and is described. Nine compounds (seven which form known hydrates and two which do not form hydrates) were tested successfully to demonstrate the utility of the method. A preferred cycle (25°C→40°C→5°C→25°C over 6 h) and solvent system (acetonitrile-water) were identified. The method needs approximately 15-20 mg, in most cases, of the compound and finds applicability in early stages of drug development (late lead-development to early candidate selection).