Abstract: In the past, Cefotaxime inhibited greater than 90% of enteric bacilli at a minimum inhibitory concentrations of less than or equal to 0.5 microgram/ml. But with the emergence of ESBL (Extended Spectrum Beta Lactamase) producing bacteria the activity of cefotaxime became questionable. So the objective of this study was to see the in-vitro efficacy of cefotaxime against common clinical isolates in this hospital. 207 culture positive samples from different sources (urine, sputum, pus and blood) were processed. Isolation and identification of microorganism was done by standard microbiological procedure and antibiotic susceptibility testing was done by Kirby Bauer disc diffusion method, MIC was calculated by E-test strip (HiComb MIC Test) and interpreted following CLSI guidelines. The sensitivity of different isolates was found to be as follows: Staphylococcus aureus 66-70%, Enterobacteriaceae (ESBL non producers) 50-75%, Moraxella 91% whereas Streptoococcus pneumoniae and Haemophilus influenzae were 100% sensitive against cefotaxime. Acinetobacter spp however was 33-75% sensitive against cefotaxime. The MIC90 of all the isolates were within the sensitive range.