A sensitive and selective RP-HPLC method is described for the determination of stability in Acetaminophen and Tramadol dosage forms. Chromatographic separation was achieved on a C18 column using mobile phase consisting of a mixture of mixed Phosphate buffer pH: 3.4 Acetonitrile (30:70v/v/v), with detection of 236nm and flow rate at 1mL/min. Linearity was observed in the range 100-300 µg /ml for Acetaminophen (r2 =0.994) & 10-30µg /ml for Tramadol (r2 =0.994) for the amount of drugs estimated by the proposed methods was in good agreement with the label claim. No chromatographic interference from tablet excipients was found. The proposed methods were validated. The force degradation of the drugs was assessed by different environmental conditions. Recovery experiments indicated the absence of interference from commonly encountered pharmaceutical additives. The method was found to be precise as indicated by the repeatability analysis, showing %RSD less than 2. All statistical data proves validity of the methods and can be used for routine analysis of pharmaceutical dosage form.