The use of transmission Raman spectroscopy for quantitative assessment of pharmaceutical tablets using different multivariate approaches was investigated. Although Raman spectroscopy is most often used in backscatter geometry, in this paper a transmission approach was utilized, where the Raman scattered light is detected at the back side of the tablets. Raman spectra were recorded using a dispersive spectrometer with a 785 nm excitation laser and a typical exposure time of 10 s. The tablets were loaded to a 32-position sample rack and measured by an automated procedure. Tablets with variation in content of paracetamol were manufactured. The data were evaluated with respect to the content of paracetamol, using partial least squares (PLS) and multivariate curve resolution (MCR). In addition, classical least squares (CLS), curve fitting and peak ratios were included for comparison. MCR, CLS and PLS gave comparable results with relative prediction errors for an independent test set in the range of 2.4–3.4%. Curve fitting and peak ratios gave higher prediction errors, typically around 4 and 6%, respectively. Interestingly, quantitative models based on only two samples in the calibration sets resulted in almost as good results as if half of the available tablets were included in the calibration. Due to the simple calibration models and the selective Raman spectra, the loadings and spectra were easy to interpret for all the multivariate methods used in this paper. The implications for content uniformity analysis by using transmission Raman in this simplified approach are discussed. Copyright © 2010 John Wiley & Sons, Ltd.