This paper presents an experimental study of flow boiling performance in Ω-shaped reentrant copper microchannels for the efficient cooling of high heat flux devices. Three reentrant copper microchannels (RCMs) with different hydraulic diameters, i.e., 590, 781 and 858μm, were fabricated via micro wire electrical discharge machining (EDM) process. The channel size effects on flow boiling characteristics of such unique microchannels, i.e., two-phase heat transfer, pressure drops and two-phase flow instabilities, were accessed in order for the design optimization. Flow boiling tests were conducted utilizing the coolant of deionized water at inlet subcoolings of 10°C and 40°C. Test results showed that the reentrant copper microchannels presented a non-monotonic dependence of boiling heat transfer on microchannel size, whereas two-phase pressure drop can be reduced with the increase in microchannel size. Reentrant copper microchannels with the medium hydraulic diameter of 781μm were considered to be the optimum to achieve the best flow boiling performance, as they presented the maximum heat transfer rates and moderate pump power, as well as their superiority to alleviate the severe two-phase flow instabilities.