Purpose The purpose of this study is three-dimensional flow and heat transfer investigation of water/Al2O3 nanofluid inside a microchannel with different cross-sections in two-phase mode. Design/methodology/approach The effect of microchannel walls geometry (trapezoidal, sinusoidal and stepped microchannels) on flow characteristics and also changing circular cross section to trapezoidal cross section in laminar flow at Reynolds numbers of 50, 100, 300 and 600 were investigated. In this study, two-phase water/Al2O3 nanofluid is simulated by the mixture model, and the effect of volume fraction of nanoparticles on performance evaluation criterion (PEC) is studied. The accuracy of obtained results was compared with the experimental and numerical results of other similar papers. Findings Results show that in flow at lower Reynolds numbers, sinusoidal walls create a pressure drop in pure water flow which improves heat transfer to obtain PEC < 1. However, in sinusoidal and stepped microchannel with higher Reynolds numbers, PEC > 1. Results showed that the stepped microchannel had higher pressure drop, better thermal performance and higher PEC than other microchannels. Originality/value Review of previous studies showed that existing papers have not compared and investigated nanofluid in a two-phase mode in inhomogeneous circular, stepped and sinusoidal cross and trapezoidal cross-sections by considering the effect of changing channel shape, which is the aim of the present paper.