Object: The aim of this study was to compare seizure and memory outcome in patients with medically refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) treated using an anterior temporal lobectomy (ATL) or a selective amygdalohippocampectomy (SA). Methods: Surgical outcome data were prospectively collected for 2 to 11 years in 161 consecutive patients with MTLE/HS. Eighty patients underwent an ATL and 81 an SA. Seizure control achieved with each technique was compared using the Engel classification scheme. Postoperative memory testing was performed in 86 patients (53%). At the last follow up, 72% of the patients who had undergone an ATL (mean follow up 6.7 years) and 71% of those who had undergone an SA (mean follow up 4.5 years) were seizure free (Engle Class IA). Estimated survival in patients in Engel Classes I, IA, and I and II combined did not differ between the two surgical techniques. Preoperatively, 58% of the patients had verbal memory scores one standard deviation (SD) below the normal mean. One third of the patients with preoperative scores in the normal range worsened after surgery, although this outcome was not related to the surgical technique. In contrast, one third of those whose preoperative scores were less than −1 SD experienced improvement after surgery. Nine (18%) of the 50 patients whose left side had been surgically treated improved their verbal memory scores by more than one SD. Seven (78%) of these nine underwent an SA (p = 0.05). Conclusions: Both ATL and SA can lead to similar favorable seizure control in patients with MTLE/HS. Preliminary data suggest that postoperative verbal memory scores may improve in patients who undergo selective resection of a sclerotic hippocampus in the dominant temporal lobe.