At sufficiently high Reynolds numbers, laminar flows in tortuous channels become unsteady. A computational fluid dynamics methodology is developed to study transient, laminar flow and heat transfer in a periodic zigzag channel with a semi-circular cross-section. The computational domain consists of seven repeating zigzag units with smoothly joined inlet and outlet sections. Reynolds numbers ranging from 400 to 800 and Prandtl numbers ranging from 0.7 to 20 are examined for constant wall heat flux and constant temperature thermal boundary conditions. Simulation results show that the flow reaches a "developed" state after around three units, where the local velocities fluctuate with time but give well defined average heat transfer rates and pressure loss. The power spectra of the velocity at monitor points located periodically along the channel also become very similar. Significant heat transfer enhancement is observed in the transient regime studied, which is accompanied by a modest pressure-drop penalty, both of which increase with increasing Reynolds number. Vortex structures are visualized at different simulation times and Reynolds numbers and it is found that with increasing Reynolds number, vortices with smaller length-scale are generated, which contribute largely to the enhancement of heat transfer. The results for different Prandtl numbers show that the heat transfer enhancement is proportional to Pr-1/3. The Nusselt number for the T boundary condition is found to be always higher than that for the H2 boundary condition. (C) 2014 Elsevier Ltd. All rights reserved.