The efficacy of Mueller Hinton agar over Nutrient agar in terms of antibiotic sensitivity testing for optimal antibiotic response by selected clinical bacterial pathogens was carried out in this study. Clinical bacterial pathogens used for the study were Pseudomonas aerµginosa, Enterococcus spp, Escherichia coli and Klebsiella pneumoniae. Standard and locally manufactured antibiotic discs used were by Abtek Biologicals Ltd, Liverpool and Maxicare Medical Laboratory, Nigeria respectively. Antibiotic sensitivity testing (AST) was by agar diffusion method. Pure cultures of each isolate were subcultured on sterile Mueller Hinton agar (MHA) and Nutrient agar (NA) media after which the standard and locally manufactured discs were aseptically impregnated on the media. All inoculated plates were incubated at 37oC for 24hrs aerobically after appropriate labeling. Zones of inhibition were measured by standard methods and recorded. On Nutrient agar, standard and locally produced ciprofloxacin, ofloxacin, gentamycin and amoxicillin/clavulanic acid discs did not produce zones of inhibition significantly different from each other at both 95% and 99% confidence intervals (P ˃ 0.05 and P ˃ 0.01). On Mueller Hinton agar, standard and locally manufactured ciprofloxacin, ofloxacin, gentamycin and amoxicillin/clavulanic acid discs produced zones of inhibition that were significantly different from each other at 95% confidence interval (P ˂ 0.05). Standard and local ciprofloxacin, ofloxacin, gentamycin and amoxicillin/clavulanic acid discs produced zones of inhibition on MHA and NA which were not significantly different (P ˃ 0.05 and P ˃ 0.01). Standard discs used recorded better zones of inhibition on MHA compared to the local discs. Standard and local discs zones of inhibition on MHA was however not significantly different from those recorded on NA (P ˃ 0.05). Standard discs therefore, did not produce better zones of inhibition over local discs on MHA and on NA. On the whole, the use of MHA for antibiotic sensitivity testing did not record greater (better) zones of inhibition than those recorded on NA except for standard ciprofloxacin, ofloxacin and gentamycin discs over the corresponding local discs on MHA only. Findings did not convincingly establish better performance of standard discs over local discs whether used on MHA or NA. Further studies in this direction is recommended.