Aspirin is a drug that has been used for widely for more than a century. Numerous stability-indicating analytical methods have been reported over the years. A new stability indicating method was developed for the accurate quantitation of aspirin in tablets using the partial least squares calibration algorithm. This method is specific for the determination of aspirin and its main degradation product; salicylic acid in tablets using ultraviolet spectrophotometry. The calibration matrix needs only 13 binary solutions and the method showed good linearity from 30 to 70 µg/ml for aspirin and 0 to 40 µg/ml for salicylic acid. Moreover, a full validation according to the International Council of Harmonization guidelines was carried out covering precision, recovery, sensitivity, sample stability and tolerance. The method was applied to developed and commercial aspirin tablets. The proposed method represents a reliable choice to be used as a routine method for quality control of newly manufactured products.