Molecular imprinting, a technique that allows for preparation of adsorbents with sites tailored for recognition of a particular molecule, continues to grow because it holds promise for several areas including separations. A key fundamental aspect in forming a molecular imprinted polymer (MIP) is the ability to optimize the amount of functional monomer relative to template used for the polymerization. In this paper, isothermal titration calorimetry (ITC) was used to predict the optimum functional monomer concentration for preparing an MIP for the drug, cinchonidine. Calorimetric titrations of cinchonidine with the functional monomer, methacrylic acid, suggested that a methacrylic acid–cinchonidine hydrogen bonded complex of minimum energy exists for solutions of 4:1 mol/mol of the monomer relative to the template. When this ratio of functional monomer to template was utilized for the MIP synthesis, the resulting polymer displayed significantly better selectivity for cinchonidine than polymers prepared with lesser or greater amounts of methacrylic acid. This observation is explained in terms of a balance that was achieved in the monomer–template equilibrium during the polymerization. This balance maximizes the favorable hydrogen bonding interactions with the template during the polymerization that yields the selective sites, but minimizes the use of excess monomer, which leads to non‐selective sites on the polymer. The results within suggest that ITC can be a valuable tool in the syntheses of MIPs.