A simple, accurate and precise chemometrics assisted UV-visible Spectrophotometric determination of triple combination commercial preparation containing ramipril (RA), aspirin (AS) and atorvastatin calcium (AT) has been proposed. The spectra of the component mixtures under investigation show substantial overlap. Resolution of the mixtures under investigation has been accomplished mainly by using one of the chemometrics methods, classical least squares regression method (CLS). CLS method does not need prior graphical treatment of the overlapping spectra of the three drugs in a mixture. Here wavelength selection is done by trial and error method. For chemometric calibrations a concentration set of the mixture consisting of the three drugs in methanol was prepared. The absorbance data were measured in the range of 210 - 340 nm at an interval of 0.1 nm. The CLS method uses 1.0 - 5.0, 10.0 - 50.0 and 2.0 - 10.0 μgmL -1 of ramipril, aspirin and atorvastatin calcium respectively for calibration. The developed calibrations were tested for the synthetic mixtures (prediction set) consisting of three drugs and the proposed method was successfully applied for the determination of the three drugs in commercial formulation. The results obtained were of high accuracy and without interference from commonly encountered excipients and additives, this is evident from the statistical validation results. Good recoveries were obtained with both synthetic mixtures and commercial formulation. Therefore this method can be routinely used in the analysis of the said combination in quality control laboratories. © RJPT All right reserved.