This study was performed to determine the stability of liquid-filled matrix ionization chamber (LiFi-type) electronic portal imaging devices (EPID) for dosimetric purposes. The short- and long-term stability of the response was investigated, as well as the importance of factors influencing the response (e.g., temperature fluctuations, radiation damage, and the performance of the electronic hardware). It was shown that testing the performance of the electronic hardware as well as the short-term stability of the imagers may reveal the cause of a poor long-term stability of the imager response. In addition, the short-term stability was measured to verify the validity of the fitted dose-response curve immediately after beam startup. The long-term stability of these imagers could be considerably improved by correcting for room temperature fluctuations and gradual changes in response due to radiation damage. As a result, the reproducibility was better than 1% (1 SD) over a period of two years. The results of this study were used to formulate recommendations for a quality control program for portal dosimetry. The effect of such a program was assessed by comparing the results of portal dosimetry and in vivo dosimetry using diodes during the treatment of 31 prostate patients. The improvement of the results for portal dosimetry was consistent with the deviations observed with the reproducibility tests in that particular period. After a correction for the variation in response of the imager, the average difference between the measured and prescribed dose during the treatment of prostate patients was -0.7%+/-1.5% (1 SD), and -0.6%+/-1.1% (1 SD) for EPID and diode in vivo dosimetry, respectively. It can be concluded that a high stability of the response can be achieved for this type of EPID by applying a rigorous quality control program.