Randomly generated heat flux transients affect the reliability of advanced integrated circuits and can induce severe nonlinearity in the device response, resulting in the degradation of a gate dielectric in metal oxide field effect transistors (MOSFETs). The effect of high heat flux transients on MOSFET operation and mitigation, using single-phase and two-phase on-chip microfluidics, is reported in this paper. A prototype comprising monolithically integrated MOSFETs, resistance temperature detector (RTD) arrays, simulated transient source (microheaters) and microfluidic networks was developed. The application of a 10 s transient (153 W cm-2) led to the degradation of subthreshold swing (S) from 120 to 240 mV/decade. However, in the presence of water flow, effective mitigation of S (up to 75%) is observed. The rate of mitigation is higher at lower flow rates because of the higher heat-transfer efficiency for two-phase flow. Thus, an appropriate selection of flow parameters can lead to optimized cooling. Additionally, we propose a strategy to localize the transient heat sources based on the temperature profiles generated using an on-chip, distributed RTD sensor array. The proposed methodology can be applied in practical integrated circuits for localization and characterization of heat sources leading to modifications in the circuit design or process integration steps. © 2011 IOP Publishing Ltd.