Databases are used to screen for warfarin-medication interactions. We measured the reliability and validity of 5 databases. Databases were queried for 30 medications identified as having varying degrees of interactions with warfarin in a recent systematic literature review. Reliability was measured by the percentage agreement between the databases for each interaction and validity was measured by agreement between each database and the systematic literature review. All of the databases and the systematic review agreed on 14 medications (47%). There were 5 medications (17%) where all databases reported an interaction, but no interaction was noted by the systematic review. The databases did not agree on the remaining 11 medications (37%). Four of these interactions were of moderate or greater clinical significance. These commonly used databases frequently do not agree on the occurrence of warfarin-medications interactions, and some interactions identified by the best clinical evidence were not identified in several databases.