Nanofluids are stable dispersions of ultrafine or nanoscale metallic, metal oxide, ceramic particles in a given base fluid. It is reported that nanofluids register an extraordinarily high level of thermal conductivity, and thus possess immense potential in improvement of heat transfer and energy efficiency of several industrial applications including vehicular cooling in transportation, nuclear reactors, and microelectronics. The key issues with nanofluids are: (i) a robust, cost-effective and scalable method to produce nanofluids to industrial scale has not yet been developed, (ii) stability in industrial applications is not yet established, and (iii) meaningful data in flow based heat transfer process do not exist. The present work attempts to address all these three issues. We have developed an in-situ technique for preparation of stable nanofluids by wet-milling of the metal oxide powder in the base fluid, and in the presence of a suitable dispersant. The nanofluids thus produced are tested for heat transfer efficiency under flow conditions in double pipe heat exchangers. Alumina nanofluids have been found to show enhancements of around 10–60% for various base fluids flown under different flow conditions. Thermal enhancements have been found to depend on the flow-rate, particle concentration, type of base fluid, and material of the thermal contact surface of the heat exchanger. The nanofluids thus obtained exhibit sustained stability (>30 months) and their stability remains unaltered for several heating-cooling cycles.