An isothermal calorimeter is typically used to measure the heat production associated with cement hydration on a sample maintained at a constant temperature. The produced heat is considered proportional to the reaction rate. Therefore, the degree of hydration of a cement paste can be precisely tracked as a function of time. In this study, we first aimed to understand the limitations of the instrument. In particular, we focused on the isothermal assumption by studying the effects of heat capacity and initial temperature differences of the reference and studied samples, that play a role at early time. Next, cement pastes were tested. Both in-situ and external mixing protocols were adopted, and heat flow measurements were monitored for cement pastes prepared at initial water-to-cement mass ratios (w/c) of 0.35, 0.40, 0.42, 0.45, and 0.55. The first peak appeared immediately after the cement was mixed with water. The second peak appeared at about 6 to 9 hours. The initial water-to-cement mass ratio influenced the time of the second value of peak heat flow. At w/c=0.35, the time was shorter than that at w/c=0.55. Finally, we recommend a protocol that reduces the influence of thermal disturbances, including guidance for sample loading and heat capacity matching.