A model drug release study on the ingress of water and Kokubo simulated body fluid (SBF) into poly(2-hydroxyethyl methacrylate) (P(HEMA)) and its copolymers with tetrahydrofurfuryl methacrylate (THFMA) loaded with vitamin B12 was undertaken over the temperature range 298–318 K. The polymers were studied as cylinders and were loaded with either 5 or 10 wt-% of the drug. The drug release from the polymers was found to follow a Fickian diffusion mechanism in the early stages of the drug release, with higher normalized release rates at higher temperatures and higher drug loadings. The normalized release rates were also found to be higher for the SBF solution than for water. The copolymer composition was found to have a significant effect on the rate of release of the drug, with the rate falling rapidly between HEMA mole fractions of 1.0 and 0.8, but for lower mole fractions of HEMA the normalized release rate decreased more slowly. This behaviour followed the trend found for the changes in the equilibrium penetrant contents for the copolymers.