A radiofrequency (RF) time‐domain electron paramagnetic resonance (EPR) instrument operating at 300, 600, and 750 MHz was used to image tumor hypoxia with high spatial and temporal resolution. A high‐speed signal‐averaging Peripheral Component Interconnect (PCI) board with flexibility in the input signal level and the number of digitized samples per free induction decay (FID) was incorporated into the receive arm of the spectrometer. This enabled effective and fast averaging of FIDs. Modification of the phase‐encoding protocol, and replacement of the General Purpose Interface Bus (GPIB)‐based handshake with a PCI‐based D/A board for direct control of the gradient amplifier decreased the gradient settling and communication overhead times by nearly two orders of magnitude. Cyclically‐ordered phase sequence (CYCLOPS) phase cycling was implemented to correct for pulse imperfections and cancel out unwanted constant signals. These upgrades considerably enhanced the performance of the imager in terms of image collection time, sensitivity, and temporal resolution. We demonstrated this by collecting a large number of 2D images successively and rapidly. The results show that it is feasible to achieve accurate, 2D pO₂ maps of tumor hypoxia with 1‐mm² resolution and minimal artifacts using a set of multigradient images within an acceptable measuring time of about 3 s, and 3D maps can be obtained in less than 1 min. Magn Reson Med 57:776–783, 2007. © 2007 Wiley‐Liss, Inc.