This study investigates the effects of ZnO, TiO2, and Al2O3 particles in the water-based fluid on entropy generation minimization in a minichannel heat exchanger. Distilled water has been chosen as the base fluid for nanoparticle volume concentration of 0.5% under the laminar and turbulent regime, steady-state flow, and the constant wall temperature. Dynamic viscosity, thermal conductivity, heat transfer, pressure drop, and total entropy generation rates of nanofluids have been experimentally analyzed in the minichannel (stainless steel), which has an inner diameter of 381 mu m and length of 20 cm, at the constant wall temperature (283 K). The nanofluid mixtures have been studied at different flow rates (from 10 to 50 ml/min) at the constant inlet (323 K) and constant channel wall temperature (283 K). The thermal performance, the pressure drop, and total entropy generation rates of the fluids have been compared for three different types of nanofluids. Maximum heat transfer enhancement of 16.04% was obtained using water-based Al2O3. Results have shown that three nanofluids have less dimensionless entropy generation than pure water. In addition, compared to pure water with these three nanofluids, the minimum value of the total entropy generation has been obtained for Al2O3 with 5.54%.