Cefixime is a third generation broad spectrum cephalosporin used against many strains of bacteria. It is widely used in oral formulations as suspension and tablets. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for oral use in many clinical conditions along with cefixime. The aim of the current study was to determine the effect of interaction between cefixime and NSAIDs on their availability in simulated intestinal environment. First the availability studies of standard cefixime and NSAIDs were performed by in vitro dissolution test, in buffer pH 7.4 at 37OC. Later cefixime along with each NSAID was individually subjected to dissolution test in buffer pH 7.4 and availability of each drug was determined using UV-Visible spectrophotometer. The results obtained from the two sets of experiment were compared to determine the change in drug availabilities after interaction and analyzed statistically by t test. The results indicate highly statistically significant interaction between cefixime and diclofenac sodium, where the availability of cefixime was significantly increased and that of diclofenac sodium was significantly decreased. Cefixime was found to greatly decrease the availability of mefenamic acid in the dissolution medium, where as the availability of tiaprofenic acid was increased. No significant interaction could be identified between cefixime and flurbiprofen. Analysis of the overall results clearly indicates that there is a potential for interaction between cefixime and NSAIDs.