Photopolymerization kinetics of doxycycline hyclate (DOX)-imprinted hydrogels were monitored by real-time Fourier transform infrared spectroscopy and differential photocalorimetry. 2-Hydroxyethyl methacrylate-based hydrogels were synthesized by using ethylene glycol dimethacrylate as a cross-linker, acrylic acid (AA) as a functional monomer, and 2,2-dimethyl-2-hydroxy acetophenone as a photoinitiator. For imprinting DOX in hydrogels, the molar ratio of template to functional monomer (DOX:AA) was chosen as 1:8 and 1:16. The polymerization was achieved at two different initiator concentrations. The conversion and reaction rate were calculated as a function of the molar ratio of template, and the results were compared to those of nonimprinted ones. In order to reveal the effect of DOX on the photoinduced radical polymerization, thermal polymerization was also performed for imprinted and nonimprinted hydrogels by using 2,2'-azobis(2,4-dimethyl-pentanenitrile) as a thermal initiator. All results showed that there is a significant effect of DOX concentration on the conversion and reaction rate of the photopolymerization reaction. The conversion and reaction rate decreased during photopolymerization when the template concentration increased in the monomer mixture.