A simultaneous estimation of RP-HPLC method was developed and validated for the estimation of Nimesulide, Cetrizine and Pseudo ephedrine HCl in tablet dosage form using C18 column (250mm 4.6mm, 5mm) with mobile phase consisting of Methanol: Water (65:35v/v) with a  flow rate of 1.0ml/min (UVdetection 220nm). Linearity was observed over the concentration range 0.1–5 µg/ml (R2=0.996) with regression equation y = 0.501x + 0.043 for Nimesulide and for Cetrizine 0.1–5 µg/mL (R2=0.994) with regression equation y = 0.4519x + 0.1656 and PseudoephidrineHcl 0.1–5 µg/mL (R2=0.997) with regression equation y = 0.3554x + 0.0088. The method was validated as per ICH guidelines.