A simple, sensitive, rapid, robust and reproducible method for the simultaneous determination of ceftriaxone and vancomycin in formulation was developed using reverse phase high performance liquid chromatographic method. The analysis was performed on C8 (250×4.6 mm, 5 μm) column with a mobile phase consisting of 0.01 M of potassium di hydrogen ortho phosphate and 0.01M of disodium hydrogen phosphate buffer (pH 4.2), methanol in the ratio of 70:30 (v/v) with a flow rate of 1ml/min. The analyte was examined with UV detector at 298 nm. In the developed method vancomycin elutes at 2.7 min and ceftriaxone at 3.7 min. The proposed method is having linearity in the concentration range from 20-100 μg/ml of ceftriaxone and 10-50 μg/ml vancomycin. The method was validated with respect to system suitability, precision, linearity, limit of detection (LOD) and limit of quantification (LOQ), accuracy, recovery, robustness, stability. The proposed method can be readily utilized for determination of ceftriaxone and vancomycin.