Lubricant in heat exchangers acts as a contaminant and it affects the heat transfer and pressure losses. Nanolubricants, that is, nanoparticles dispersed in lubricant oils, have shown potential to augment heat transfer rates in refrigerant direct-expansion evaporators. However, the mechanisms of such heat transfer enhancements are still unclear. Experiments were conducted to study the saturated two-phase flow boiling heat transfer phenomena of refrigerant R410A with two nanolubricants in a 9.5 mm I.D. smooth copper tube. The nanolubricants had non-spherical ZnO nanoparticles and spherical γ-Al2O3 nanoparticles dispersed in Polyolester (POE) lubricant. Al2O3 nanolubricant shared similar thermal conductivity in the wet state as that of ZnO nanolubricant. However, Al2O3 nanolubricant had about 15% higher heat transfer coefficient that ZnO nanolubricant. The heat transfer coefficients of R410A-nanolubricant mixtures degraded by about 20% with respect to that of the R410A, but improved at higher vapor qualities. The experiments showed that long-term flow boiling testing of R410A and nanolubricant mixtures resulted in a continuous gradual increase of the heat transfer coefficient. In smooth copper tubes, nanoparticle deposition on the tube inner wall, which was experimentally observed, and the near wall interactions of nanoparticles promoted additional nucleate boiling and led to such increase.