The objective of this study was to check the capability of UV spectrophotometric method for the simultaneous determination of Emtricitabine and Tenofovir Disoproxil Fumarate in tablet dosage form by Principal Component Regression(PCR) and Partial Least Squares(PLS) multivariate calibration methods. A double beam UV spectrophotometer (Jasco V-730) with 1cm quartz cell with 1nm data interval and scanning speed of 400nm/min was used in the study. The optimized wavelength range selected was 225-275 nm. The data obtained was processed using UnscramblerX (10.5)(64bit) software. The developed models showed good results over theconcentration range of 6-36 µg/ml for Tenofovir Disoproxil Fumarate and 4-24 µg/ml for Emtricitabinewith co-relation coefficient greater than 0.995 and %RSD less than 2%. The accuracy studies show % recovery within limits. The method was validated as per ICH Q2(R1) guideline.