A simple, rapid, selective, precise and economical RP-HPLC method has been developed and validated for the quantitative estimation of Cefixime and Ofloxacin in pharmaceutical preparation. Chromatographic separation was achieved on using Kromasil C18 column (250 mm x 4.6 mm, 5μm i.d) analytical column with mobile phase consisting of 40:60 v/v mixture of Ammonium Acetate buffer: Acetonitrile. flow rate was 1.0 ml/min and the detection of wavelength was 294nm. In the developed method Cefixime and Ofloxacin elute at typical retention times of 2.26 min and 3.24 min respectively. The proposed method has permitted the quantification of Cefixime in the linearity range of 60 -140 μg/mL and for Ofloxacin in the range of 60 - 140 μg/ mL. The intraday and interday precision was found less than 2% and the LOD and LOQ for Cefixime were found to be 0.146 - 0.44 μg/mL and for Ofloxacin were found to be 0.16 - 0.49 μg/mL respectively. The validated optimized method for analysis of Cefixime and Ofloxacin as per ICH Q2B guidelines was found to be simple, precise and reproducible. Undoubtedly present developed easiest, rapid and validated method can be applied routinely for the analysis of drugs in bulk as well as tablet dosage form.