The precision with which the dissociation constant,K_D, can be obtained from isothermal titration calorimetry depends on, among other factors, the concentrations of the interacting species. The so-called c value—the ratio of analyte concentration to K_D—should fall in the range of 1 to 1000 for reliable K_D determination. On the basis of simulated, noise-free data, Biswas and Tsodikov [5] recently suggested an optimal c value of 5 to 20. By contrast, we find an optimum at c>40 on determining the K_D confidence intervals through simulations containing noise levels typical of state-of-the-art microcalorimeters.