A multiple wavelenght spectrophotometric method was validation for determination of binary mixtures acetominophen and caffein that available in antipyretic and analgetics. The aim of the research to determination of acetominophen and caffeine combinations in commercial tablets,using spectrophotometry ultraviolet with multiple wavelength method. The determination of commercial tablet that content 600 mg acetominophen and 50 mg caffeine can use the spectrophotometry ultraviolet with multiple wavelength method, in the solvent 0.1 N hydrochloride acid at the six wavelengths are 223 nm; 243,8 nm; 254 nm; 258 nm; 262 nm; and 271 nm then data calculation with matrix operation. The results of research was exhibited that acetominophen in tablet are 91.75% ± 0.31% and caffeine are 99.49% ± 0.38% and percent coefficient variation of acetominophen are 0.40% and caffeine are 0.36%. So it can be concluded that the spectrophotometry ultraviolet with multiple wavelength method in the present investigation was found to be simple, sensitive, accurate and precise and can be successfully applied for determine the content of acetominophen and caffeine in commercial tablet.