The objective of this study was to investigate the effect of physiological conditions on the dissolution rate of acetylsalicylic acid (ASA) from two commercial brands compared against compendial tests. All parameters of the analysis were chosen according to ICH (Q2(R1)) guidelines and were validated statistically. The maximum wavelength (λ max ) and absorptivity (ε) for ASA were determined in different solvents at different pH values (6.8 and 4.9) by a validated UV-Vis spectrophotometric method. When ethanol (EtOH) was used as co-solvent, ε was found to be 3.15, and when 0.1 N NaOH was used, ε was 18.50. Dissolution tests were conducted according to pharmacopeia specifications; however, the lack of a direct specification in determining ε in the pharmacopeia has permitted enormous probabilities of employing different solvents. Herein, when NaOH was used to dissolve ASA, ε was calculated to be 18.50, and upon conducting compendial dissolution tests for enteric-coated tablets, only 20% of ASA was released after 4 h. When analyzing the same data using ε of 3.15 (calculated from dissolving ASA in EtOH), the amount of released ASA was found to be 95% after 2 h. Furthermore, the effect of a fed and fasted state pH was not significant on the dissolution rate, and both brands met the compendial requirements.