This study reports experimental and Computational Fluid Dynamics (CFD) investigations of the laminar convective heat transfer coefficient of Al2O3/water nanofluids in a circular tube under uniform and constant heat flux on the wall. Three different models including a constant physical properties single-phase (CP-SP) model, a variable physical properties single-phase (VP-SP) model and a discrete particles two-phase model were developed. Particle agglomeration and cluster size distribution were considered in the two-phase model. Experimental and simulation results showed that the thermal performance of nanofluids is higher than that of the base fluid and the heat transfer enhancement increases with the particle volume concentration and Reynolds number. Furthermore, higher heat transfer coefficients were detected in the case of the VP-SP model and the two-phase model. The results demonstrated that the two-phase model prediction and experimental data match significantly and that the model can be employed with confidence for the prediction of any type of nanofluid.