In this work, a simple and rapid analytical procedure was proposed for simultaneous determination of acetylsalicylic acid (ASA), paracetamol (PRC, also known as acetaminophen) and caffeine (CAF) in pharmaceutical formulations based on multivariate calibration and UV spectrophotometric measurements (210-300 nm). The calibration set was constructed with nine solutions in the concentration ranges from 10.0 to 15.0 microg x ml(-1) for ASA and PRC and from 2.0 to 6.0 microg x ml(-1) for CAF, according to an experimental design. The procedure was repeated at four different pH values: 2.0, 3.0, 4.0 and 5.0. Partial least squares (PLS) models were built at each pH and used to determinate a set of synthetic mixtures. The best model was obtained at pH 5.0. An N-way PLS model was applied to a three-way array constructed using all the pH data sets and enabled better results. This calibration model provided root mean squares errors of prediction (RMSEP) from 11.5 to 35% lower than those obtained with PLS at pH 5.0, depending on the analyte. The results achieved for the determination of these drugs in commercial tablets were in agreement to the values specified by the manufactures and the recovery was between 94.7 and 104.5%.