Vibrational spectroscopic methods were developed for quantitative analysis of Form II of clopidogrel bisulphate in Form I and Form II polymorphic mixtures. Results show that both IR and Raman spectroscopy combined with chemometrics are suitable to quantify low levels of Form II in Form I, down to 2 and 3%, respectively, with less than 1% limit of detection. Different preprocessing and multivariate methods were applied for spectral processing and were compared to find the best chemometric model. Common problems of quantitative vibrational spectroscopy in the solid phase are discussed; and procedures appropriate to eliminate them are proposed.