Objective: To develop rapid, accurate, reproducible, validated and economical difference spectroscopy method for the simultaneous determination of moxifloxacin (MFN) and cefixime (CEF) in tablet dosage forms.Methods: The method comprised the measurement of the absorbance of a solution of the tablet extract in 0.1 M NaOH relative to that of an equimolar solution in 0.1 M HC1 at 254 nm for MFN and 292 nm for CEF. The presence of identical isosbestic points for pure drug solutions and tablet extracts indicated the non-interference of excipients in the absorption at these wavelengths.Results: The method was found to be linear over the concentration range of 10-50 μg/ml for CEF and 4-20 μg/ml for MFN. Accuracy was found to be in the range of 99.91-101.18%. Relative standard deviation for precision and intermediate precision was found to be less than 2%. The developed method was successfully applied for the simultaneous estimation of Moxifloxacin and Cefixime in tablet formulation. The results obtained from the validation experiments prove that the developed method is suitable for routine analysis.Conclusion: This method is simple, selective, linear, precise, and accurate and sensitive hence can be successfully employed for the routine quality control of dosage forms containing both the drugs in pharmaceutical industries.Â