The copolymerization reactions of acrylic systems of biomedical interest, 2-hydroxyethyl methacrylate (HEMA)/2-acrylamido-2-methylpropanesulfonic acid (AMPS) and N,N-dimethylacrylamide (DMAA)/AMPS, have been analyzed by H-1 NMR. A new methodology is described for the determination of the reactivity ratios based on the quantitative in situ NMR analysis in the course of the copolymerization reaction. The methodology uses the continuous change of the intensity of resonance signals assigned unambiguously to the monomers participating in the polymerization reaction with the reaction time at a given temperature. The evaluation of the monomer concentrations leads to the determination of the instantaneous feed molar fractions and the reactivity ratios, by using a solution of the differential copolymerization equation which describes the terminal model described by Mayo and Lewis. Two approaches to obtain the reactivity ratios by nonlinear fitting of the experimental data to this integrated form are described. The first incorporates the initial conditions as third parameter in the optimization (the values obtained are r(HEMA) = 6.81 and r(AMPS) = 0.116 for the HEMA-AMPS system and r(DMAA) = 1.50 and rAMPS = 0.40 for DMAA-AMPS), and the second uses different points as initial conditions in the integrated equation (obtaining r(DMAA) = 1.53 and r(AMPS) = 0.36, in very good agreement with the obtained by the first method). These values are in good agreement with those described in the literature and with data for copolymers prepared at low conversion analyzed by standard methods.