Abstract: The simultaneous equation approach is based on drug absorption (X, Y and Z) at the maximum wavelength of the other drug. The three wavelengths chosen for the method are Efavirenz (EFV), Emtricitabine (EMT) and Tenofovir disoproxil fumarate (TDF) λmax, respectively, 240nm, 256nm and 316nm. Then, by using different parameters, the established method was validated. For the simultaneous estimation of the ternary mixture of Efavirenz (EFV), Emtricitabine (EMT) and Tenofovir disoproxil fumarate (TDF) in combined synthetic mixture by Vierordt method or simultaneous equation method, a simple, precise, reliable, reproducible and efficient UV spectrophotometric method has been developed and validated. In 0.1 N NaOH, the standard and sample solutions were prepared. In the concentration ranges of 10-50μg/ml for EFV, 5-25μg/ml for EMT, and 5-25μg/ml for TDF, the calibration curves are linear. Recovery studies have tested the validity and reliability of proposed approaches. At three replication and three concentration stages, the recovery of added standards (80 percent, 100 percent and 120 percent) was found. The percent value means only near 100, SD and less than 2 percent RSD imply the method's accuracy. The accuracy was calculated by repeatability and intermediate precision. The effect of repeatability implies consistency over a short interval of time under the same operating environment. In laboratory variation on different days and analyst to analyst variation by distinct analysts, the intermediate precision analysis is expressed. The value of SD and the percentage of RSD less than 2 show the method's accuracy.