Numerical simulation of fully developed laminar fluid flow and heat transfer in a twisted sinusoidal wavy microchannel is presented. Twisted channel is a sinusoidal rectangular channel with progressive rotation of its cross sectional geometry in stream wise direction. 3-D, unsteady, incompressible, laminar flow model with constant wall temperature and heat flux boundary conditions are simulated using SIMPLE algorithm based finite volume method. Computational procedure has been validated using available experimental data. Extensive computations have been performed to study the thermo-hydraulic performance of twisted wavy microchannels with various amplitude to wavelength ratios and twist ratios for 300 ≤ Re ≤ 700. Results show that the twisted wavy microchannels can substantially enhance heat transfer performance with minimal pressure drop for low Re number regime compared to sinusoidal microchannels. Twisted channels of higher aspect ratio and lower waviness produced heat transfer enhancement of around 30% compared to sinusoidal wavy microchannels.