This paper presents a three-dimensional numerical analysis to study the laminar heat transfer and flow characteristics of Al2O3-water nanofluids through a flat tube at constant heat flux boundary condition. New correlation models for thermal conductivity and viscosity of Al2O3-water nanofluids are developed and verified. Based on the single-phase approach, the effects of different parameters such as nanoparticle volume concentration, nanoparticle size, Reynolds number, temperature and tube flattening on the thermal-hydraulic performance of flat tube with Al2O3-water nanofluids as working media are discussed in detail. Then, this study provides an entropy generation analysis to evaluate the overall superiority of nanofluids. Numerical results show that the addition of nanoparticle enhances the heat transfer and pressure loss of base fluid in all of the flat tubes at various Reynolds number and temperature. Both the relative average convective heat transfer coefficient and press drop can be enhanced by increasing nanoparticle volume concentration and decreasing nanoparticle size. And the heat transfer and press drop enhancements of nanofluids are more obvious at smaller Reynolds number and higher temperature. In additions, it is also detected that the thermal entropy generation is the main part caused irreversibility, and the increase of nanoparticle volume concentration and size can decrease the total entropy generation of Al2O3-water nanofluids in a flat tube. Moreover, compared to the tube flattening, nanoparticle volume concentration has a slight effect on the relative thermal-hydraulic performance between flat tubes and circular tube. (C) 2015 Elsevier Ltd. All rights reserved.