Near infrared spectroscopy has developed in the polymer industry as a tool for in-line monitoring of processes, particularly extrusion. However, little work is dedicated to the monitoring of chemical reactions involving polymer melts. In this paper, we examine the suitability of NIR spectroscopy for monitoring the chemical modification (catalyzed esterification) of a molten ethylene-vinyl alcohol copolymer by octanoic acid in a twin screw extruder. Extrusion samples are characterized off-line, for calibration purposes, for the three species of interest (i.e. unreacted acid, OH groups, and ester functions formed on the polymer backbone) by means of two techniques: H-1 NMR, allowing all three species to be quantified, and residual (free) acid titration. However, the mass balance of free acid is not straightforward, due to loss of mass by volatilization at the vent. Therefore, H-1 NMR analysis and acid titration have to be combined to allow for determination of all concentrations. Multivariate calibration is implemented here to quantify and subsequently predict the analyte concentrations by using the NIR spectroscopic data. Our calibration, based on a partial least squares regression software, provides satisfactory results in terms of correlation between actual and predicted concentrations. This work demonstrates the potential of in-line NIR spectroscopy for monitoring chemical reactions with polymer melts in extrusion.