Disintegration is the first event in the bioavailability cascade after the ingestion of immediate release tablets. Although the influence of various physico-chemical parameters of media on tablet disintegration has been investigated in depth, the role of temperature has received much less attention. Probing the effect of temperature on disintegration is important in order to understand if previous in vitro studies conducted at room temperature can be related to those performed at body temperature. Moreover, from a biorelevant point of view, a tablet could be co-ingested with a cold or hot drink, inducing transient variations of intragastric temperature; state of fever could also elevate body temperature. Here, we studied the effect of temperature on disintegration of directly compressed tablets made of disintegrants alone and in combination with commonly used diluents and binders, using an image analysis technique as well as a compendial disintegration apparatus. Our results indicate that temperature in the range of 23°C to 41°C had a positive effect on disintegration: tablets tested at higher temperatures exhibited up to 2.9-fold faster disintegration than those tested at lower temperatures. The extent of temperature effect on disintegration time was significantly influenced by the composition of the formulations. Overall, the findings of this study suggest that disintegration results obtained in vitro at room temperature can be qualitatively, but not quantitatively, compared to those obtained at body temperature. We also speculate that although temperature had a moderate influence on in vitro disintegration, the magnitude of this effect is unlikely to impact the oral bioavailability in vivo.