A new isocratic stability-indicating high-performance liquid chromatography (HPLC) method has been developed and validated for the simultaneous determination of Sildenafil (SIL) and Dapoxetine (DAP) in solid dosage form. The chromatographic separations were achieved with a Waters Xterra C18 (4.6 x 250 mm, 5 mu m) column, using a mixture of acetonitrile and phosphate 9.5 buffer (70:30, v/v) as a mobile phase, under isocratic elution mode with a flow rate of 13 mL/min, and ultraviolet (UV) detection was set at 228 nm. The oven temperature for the column was set and maintained at 25 degrees C. The method was validated according to International Conference on Harmonization (ICH) guidelines, and it demonstrated excellent linearity, with a correlation coefficient of 0.99969 and 0.99997 for SIL and DAP, respectively, over the concentration ranges of 0.25-0.75 mg/mL (SIL) and 0.15-0.45 mg/mL (DAP). The retention time (tR) was found to be 2.7 and 6.1 min for SIL and DAP, respectively. Extensive stress degradation studies were conducted by subjecting the analytes to various stress conditions of acidic and alkaline hydrolysis as well as oxidative, photolytic, and heat degradations. The method was found to efficiently separate the analytes' peaks from that of the degradation products, without any variation in their retention times. The limit of detection (LOD) and the limit of quantification (LOQ) values were 0318 and 1.060 pg/mL for SIL, 0.316 and 1.053 mu g/mL for DAP, respectively. Recovery percentages were found to be 99.07-10037% for SIL and 99.43-100.11% for DAP. The method was applied to simultaneous analysis of SIL and DAP in tablet dosage form. The proposed method is simple, rapid, selective and reproducible. It can be recommended to be used for simultaneous analysis of SIL and DAP in pharmaceutical industry.