EEG-triggered functional MRI (fMRI) offers the potential to localize the generators of scalp EEG events, such as interictal epileptiform discharges, using a biological measurement as opposed to relying solely on modelling techniques. Although recent studies have demonstrated these possibilities in a small number of patients, wider application has been limited by concerns about patient safety, severe problems due to pulse-related artefact obscuring the EEG trace, and lack of reproducibility data. We have systematically studied and resolved the issues of patient safety and pulse artefact and now report the application of the technique in 24 experiments in 10 consecutive patients with localization-related epilepsy and frequent interictal epileptiform discharges (spikes or spike wave). At least two experiments were performed for each patient. In each experiment, 10- or 20-slice snapshot gradient-echo planar images were acquired approximately 3.5 s after a single typical epileptiform discharge (activation image) and in the absence of discharges (control image). Between 21 and 50 epileptiform discharges were sampled in each experiment. The significance of functional activation was tested using the t test at 95% confidence on a pixel-by-pixel basis. Six of the 10 patients showed reproducible focal changes of the blood oxygen level-dependent (BOLD) signal, which occurred in close spatial relationship to the maximum of the epileptiform discharges in the concurrent EEG. No reproducible focal BOLD signal changes were observed in the remaining four patients. In conclusion, EEG-triggered fMRI is now a sufficiently developed technique to be more widely used in clinical studies, demonstrating that it can reproducibly localize the brain areas involved in the generation of spikes and spike wave in epilepsy patients with frequent interictal discharges.