By considering both reaction and crystallization of paracetamol as a single process for the purpose of continuous operation, the solubility for crystallization was firstly optimized, from which suitable concentrations of reagents for the reaction were then determined. The effects of water content and reaction temperature on reaction kinetics and mechanism as well as crystal properties were jointly investigated, for the first time, using chromatographic methods; paracetamol form I particles with high purity (99%) were produced with the presence of water, while 4'-acetoxyacetanilide was the main product in the absence of water.