Aspirin (acetylsalicylic acid, ASA) remains one of the most widely used analgesic and anti-inflammatory agents, making accurate and reliable quantification in pharmaceutical formulations a critical quality control requirement. Classical titrimetric assays using sodium hydroxide exploit the carboxylic acid functionality of ASA, but their lack of selectivity leads to overestimation in multicomponent formulations where organo-acidic excipients also consume the base. In this study, six commercial aspirin tablet formulations from established manufacturers were comparatively analyzed using Titrimetric, UV–Vis Spectrophotometry with multivariate calibration, and High Performance Liquid chromatographic (HPLC). Results indicates that titrimetric assays required complex stoichiometric corrections, manipulations and produced inconsistent values in formulations containing interfering acidic excipients. The Spectrophotometric method enabled rapid screening but often produced values near or below the lower pharmacopeial limits, indicating limited robustness in complex formulations. Notably, the spectrophotometry method showed high variability and marked inaccuracy in one sample (−32.8%), emphasizing its susceptibility to matrix effects. By contrast, the chromatographic (HPLC) technique provided superior resolution, precision, and accuracy, consistently yielding results within United States Pharmacopeia (USP) and British Pharmacopoeia (BP) limits. The findings also highlight the trade-off between simplicity and specificity across analytical approaches, underscoring the importance of chromatographic confirmation for regulatory compliance and stability testing, while recognizing the continued relevance of low-cost methods for routine screening in resource-limited settings.