A simple, fast and precise reverse phase, isocratic HPLC method was developed for the separation and quantification of Sildenafil and Duloxetine in pharmaceutical dosage form. The quantification was carried out using Symmetry C18-ODS 4.6X150mm, 3µm enhanced polar selectivity column and mobile phase comprised of potassium dihydrogen phosphate buffer and acetonitrile and water in proportion of ratio 30:65:5 and degassed under ultra-sonication. The flow rate was 0.6mL/min and the effluent was monitored at 244nm. The retention time of Sildenafil and Duloxetine were 4.3 and 3.4 respectively. The method was validated in terms of linearity, precision, accuracy, and specificity, limit of detection and limit of quantization. Linearity of Sildenafil and Duloxetine were in the range of 100 to 300µg/mL and 30 to 90µg/mL respectively. The percentage recoveries of both the drugs were 98.7% and 99.8% for Sildenafil and Duloxetine respectively from the tablet formulation.The method was found to be precise, accurate and specific during the study. The proposed method enables rapid quantification and simultaneous analysis of both drugs from commercial formulations without any excipients interference. The method can be used for routine analysis of marketed products of Sildenafil and Duloxetine in combined tablet formulation