Herschel�Bulkley non-Newtonian fluid flow and heat transfer are commonly encountered in chemical processing industries, such as pharmaceutical, food, oil, and gas industries. Unlike Newtonian fluid, which has been intensively studied, the flow profile and heat transfer characteristic study of this non-Newtonian fluid is relatively scarce. This may hinder further thermal technology advancement for this unique rheological fluid. This study is therefore focused on the flow and heat transfer of Herschel�Bulkley non-Newtonian fluids in heat exchangers with twisted tape insert as a passive heat transfer enhancement method. Based on the conservation principles of mass, momentum, and energy for the non-Newtonian fluid flow by considering the effect of viscous dissipation, a three-dimensional computational fluid dynamics (CFD) model was developed and validated against the available published experimental data. Once a good agreement was achieved, the validated model was then utilized to study the effect of key parameters such as tape twist ratio, flow indices, yield stress, consistency index, and generalized Reynolds number. It was found that the helical heat exchanger with twisted tape demonstrates superior heat transfer performance, illustrated by a higher Nusselt number, at the cost of a higher pressure drop. For straight tubes, however, the addition of twisted tape deteriorates the heat transfer performance, mirrored by a lower Nu and a higher pressure drop. Among the considered twist ratios, moderate and high twist ratios (less number of turns) of 7.86 and 15.73 offer the optimum balance between higher heat transfer performance and additional pressure drop. Meanwhile, it was found that increases in the studied parameters, i.e., flow indices, yield stress, consistency index, and generalized Reynolds number, have a positive impact on the heat exchanger performance, indicated by a higher performance index. Finally, friction factor and Nusselt correlations were developed as a function of fluid thermal properties and heat exchanger geometrical parameters for practical applications. © 2021 American Chemical Society