A simple, accurate, critical, and reliable RP-HPLC chromatographic method for the simultaneously determining tadalafil, avanafil, sildenafil citrate, and vardenafil hydrochloride as a mixture of drug combinations or individually. Method separations were performed on an Agilent Zorbax L1 analytical column (4.6 mm × 150 mm, 5 microns) or equivalent. Using the filtration system and ultrasonic instrument a mixture of tetrahydrofuran: methanol: phosphate buffer pH 6.5 with triethylamine was used as the mobile phase. by using a room temperature of about 25 ℃, an adjusted flow rate of about 1.5 ml/min, and an ideal wavelength of 225 nm. In the chromatographic technique, the elution time of tadalafil, avanafil, sildenafil citrate, and vardenafil hydrochloride was found to be 5.87, 9.08, 9.98, and 13.3 min, respectively, respectively, and the linearity range for tadalafil, avanafil, sildenafil citrate, and vardenafil hydrochloride (25 – 75) µg/ml. The linear Regression coefficient for the method is ≥ 0.999. The validation method exercise complies with the parameters as per ICH guidelines: text and methodology Q2 (R1) and FDA guidelines. Hence, the proposed technique was used in quality control for all quantitative analyses of tadalafil, avanafil, sildenafil citrate, and vardenafil hydrochloride which used for treatment erectile dysfunction (ED) in raw materials or other pharmaceutical dosage forms.