Abstract: Particle size reduction technologies aiming to obtain amorphous nanoparticulate systems have gained a lot of attention. Co-milling of active pharmaceutical ingredient (API) with polymers is an attractive approach for pharmaceutical industry to prepare and stabilise the amorphous state. In this study, piroxicam anhydrate form I (PRXAH I) was used as a model API and PVP25, PVP90, and Soluplus® as model polymers. Co-milling was performed both at room and low temperature. The physical stability of the obtained samples was analysed using variable temperature X-ray powder diffractometry (VT-XRPD), DSC, Raman, and FT-NIR, and further, the dissolution performance was tested in the presence of simulated gastric fluid with both at-line XRPD and on-line Raman spectroscopy. Multivariate data analyses were applied to further visualise the data. Co-milling with polymers, PVP25 and PVP90, was sufficient to produce amorphous PRX system already at room temperature. Stability of these co-milled samples was dependent on the PRXAH I–polymer ratio. Dissolution of amorphous PRX from co-milled solid dispersions was compared with the physical mixtures with the same polymers. Recrystallisation of amorphous PRX was observed in the presence of simulated gastric fluid and it was already observed within the first three minutes of testing. Both methods (XRPD and Raman) revealed that amorphous PRX crystallised as PRX monohydrate during dissolution testing. Co-milling can be considered as a suitable method for preparation of stable mixtures of amorphous PRX and polymers. Further insight into the dissolution behaviour of prepared samples was obtained with both XRPD and Raman.