Simple, green and accurate UV spectrophotometric methods were established aiming for simultaneous estimation of aspirin and esomeprazole without prior separation. These methods are zero order absorption, ratio subtraction, mean centering and absorbance subtraction. In zero order method esomeprazole was measured at 302.0 nm at which aspirin has no absorbance while aspirin was determined by a ratio subtraction at 225.0 nm after deduction of overlapping caused by esomeprazole. In mean centering, the mean centered values were estimated at 228.0 nm and 262.0 nm for aspirin and esomeprazole respectively. In absorbance subtraction method the two drugs intersect at isoabsorptive point at 237.0 nm and esomeprazole spectrum is further prolonged where aspirin has no absorbance. The isoabsorptive point can be used for their determination using calculated factor called absorbance factor. These methods are effective for estimation of aspirin and esomeprazole in dosage form. Moreover, the greenness of the suggested methods was evaluated demonstrating minimum hazardous effect on the environment.