A simple, sensitive, accurate and precise UV ‐ spectrophotometric isobastic point method for simultaneous estimation of Cefixime trihydrate and Cloxacillin sodium in tablet dosage form has been developed and validated for accuracy, precision, ruggedness, linearity and range. The wavelengths selected for estimation of drugs were 241.8 nm (isobastic point at which both drug exhibit equal absorbance) and 290.0 nm (λ_max of Cefixime trihydrate). Linearity for Cefixime trihydrate and Cloxacillin sodium were 2-20 μg/ml and 5-30 μg/ml respectively. The method gives results for high accuracy and high recovery of 99.76±0.08 and 99.38±0.22 for Cefixime trihydrate and Cloxacillin sodium respectively. % R.S.D. values for marketed formulation analysis were found to be less than 2 which indicated good precision and reproducibility of the method. The method was found to be simple, sensitive, accurate and precise.