Determination of inactivation kinetics, associated with thermal processing of foods and obtained from dynamic temperature experiments, requires carefully designed experiments, the primary element being the selection of the appropriate temperature profile along with a carefully planned sampling schedule. In the present work, a number of different dynamic temperature profiles were investigated in terms of their ability to generate accurate kinetic parameters with low confidence intervals (CIs). Although alternative models have been also tested, our work was concentrated on thermal inactivation kinetics that could be described by the classical D‐z values. A pair of D and z values was assumed, and for each temperature profile tested, concentration data at different processing times were generated through the appropriate models. Next, an error (up to ±2.5% or ±5%) was introduced on these theoretical values to generate pseudo‐experimental data, and the back‐calculation of the assumed kinetic parameters by non‐linear regression was performed. The accuracy and the 95% CIs of the estimated kinetic parameters were evaluated; joint confidence regions were also constructed to investigate parameters correlation. The effect of temperature profile pattern, level of error, number of experimental points, and reference temperature was assessed. A stepwise increasing and a single triangle‐pattern temperature profile were the best profiles among those tested. As a general observation, based on different kinetic models investigated, temperature profiles and sampling intervals that result in concentration versus time diagrams having shapes as suggested by the primary model used when isothermally applied are not considered appropriate for parameter estimation.