Objectives: The compatibility of ofloxacin with some commonly used diluents has been investigated using isothermal stability studies (IST) to allow relative ranking. Materials and Methods: The samples were prepared using three methods namely physical admixtures (with 5% added moisture), slugging and kneading in order to evaluate the effect of mechanical treatment on the physicochemical stability of drug. To further verify the results of IST fresh binary mixtures were subjected to thermal analysis and an attempt was made to correlate the results obtained from the two studies. Results: The results from both DSC and IST revealed that ofloxacin was compatible with all the diluents used in the study. Among the three methods of sample preparation used for the study, the extent of degradation was more or less same in all the three methods indicating least influence of method of sample preparation on the results of IST. Conclusions: From the study it was concluded that a better co-correlation could have been obtained had ofloxacin been more unstable with few of the excipients than rest, used in the study. This way the extent of degradation would be distinguishing enough to rank the excipients in decreasing order of stability.