We examined the efficacy of a memory difference score (DS: right minus left hemisphere memory) during the Wada test (intracarotid amobarbital procedure, IAP) for predicting seizure laterality and postoperative seizure outcome in 70 left speech dominant patients from two epilepsy centers. DS > or = 2, after addition of 1 point to the left hemisphere injection score to account for aphasia, were noted in 71.4% of patients and correctly predicted surgery side for 98.0% of these patients. The DS related significantly to seizure outcome at 1-year follow-up (p < 0.002) and correctly predicted 80% of patients who were seizure-free. Patients whose DS did not correctly predict seizure laterality more frequently required invasive studies to establish seizure onset. The relationship of the DS to laterality did not differ significantly by class of IAP memory stimuli. When seizures originate from the temporal lobe, the IAP memory DS predicts seizure laterality by assessing the functional adequacy of the involved hemisphere and is predictive of seizure control.