Brain single photon emission computed tomography (SPECT) can be a useful tool to identify the epileptogenic zone in selected patients. However, ictal SPECT during spontaneous seizures is difficult to obtain and can be expensive, due to extra hospitalization time and personnel resource utilization. The efficacy of ictal SPECT depends on the ability to inject as early as possible after the beginning of the ictal discharge and/or the occurrence of the first symptom and is challenged by the short duration and rapid propagation of seizures, especially extratemporal seizures. We studied 52 patients with drug-resistant epilepsy who underwent ictal SPECT during provoked seizures in order to demonstrate the efficacy of this technique to define the epileptogenic zone and its predictive value on surgical outcome 2 and 5 years after surgery. In our study, SPECT hyperperfusion areas and electroclinical findings co-localized within the same lobe in 40 patients. Thirty-one patients were operated; at the 2-year follow-up 25 of these patients were in Engel's class I. Eighteen of the seizure-free patients showed a co-localization between the provoked SPECT hyperperfusion areas and the epileptogenic zones. Eighteen of the 31 operated patients were followed 5 years after surgery. The surgical outcome was stable in all but one subject. All the patients who were seizure-free at the 5-year follow-up showed a co-localization between the provoked SPECT hyperperfusion areas and the epileptogenic zones. Ictal SPECT demonstrated additional diagnostic value in the identification of the epileptogenic zone in 20 patients: 11 extratemporal (4 probably symptomatic and 7 lesional), 1 temporal plus (probably symptomatic), and 8 temporal (1 probably symptomatic and 7 lesional). Statistical analysis showed a significant association between the concordance of SPECT hyperperfusion areas to epileptogenic zones and freedom from seizures as assessed 5 years after surgery.