Three chemometric techniques were described for the analysis of pyridoxine hydrochloride and thiamine hydrochloride within a vitamin combination in the presence of spectral interferences. For these techniques, the training set was prepared by using synthetic mixtures containing two vitamins in multiple possible combinations for the range of 8–40 μ/mL in 0.1 M HCl. The absorbance values for the training set were obtained by direct measurements at 18 wavelengths in the region 222–305 nm for the zero order spectra. The numerical values were calculated by using the ‘Maple V’ software. Mean recoveries and relative standard deviations for the principal component analysis, classical least squares and inverse least squares techniques were found as 100.7% and 0.95%; 100.5% and 1.38% and, 99.3% and 1.04 for pyridoxine hydrochloride; and 99.7% and 1.03%; 99.1% and 1.05% and, 99.6% and 1.58% for thiamine hydrochloride, respectively. These three chemometric techniques were successfully applied to vitamin tablets marketed in Turkey. The results were compared with each other and good coincidence was observed.