New stability- indicating Reverse Phase High Performance Liquid Chromatography was developed for the simultaneous determination of Ceftalazone and Tazobactum in bulk and pharmaceutical formulations. This method was accurate, precise and sensitive for the simultaneous analysis of Ceftalazone and Tazobactum. Optimization of the mobile phase can be done by using different combinations of organic solvents and buffer solutions were used on Inertsil ODS C18 (150 mm × 4.6 mm, 5 μ) column. The OPA Buffer: Acetonitrile buffer mixture of 53:47% v/v was a selected method with a flow rate of about 1.0 ml/min. The advantages of this method were shortest retention time, good shapes peaks and very lowest noise with baseline stability. The retention times of Ceftalazone and Tazobactum are 2.058 and 3.709 min respectively. Quantitative linearity of Ceftalazone and Tazobactum was obeyed in the concentration range of 25-150 and 12.5-75 μg/ml respectively. The detection and quantitation limits were found to be 0.36 μg/mL and 1.09 μg/mL (Ceftalazone); 0.06 μg/ mL and 0.19 μg/ml (Tazobactum) respectively. It represents the sensitivity of the method. The higher accuracy of our established method was found due to the highest recovery percentage. The excipients are used in the injection formulations can’t interfere with the determination of the drugs by the proposed RP-HPLC method. It arises due to the absence of interfering peaks found in that chromatogram.