INTRODUCTION: Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally-invasive potential alternative to open resection for mesial temporal lobe epilepsy (MTLE), but outcome data are limited (Willie et al, 2014). Here we present data on effectiveness, safety, and related findings collected from investigator-initiated, prospective, observational studies at 7 centers. METHODS: Fifty-one subjects who met entry criteria for surgical treatment of MTLE were enrolled in IRB-approved prospective data collection and underwent SLAH. Screening and follow-up visits were arranged per protocol at a given center, typically at 1, 3, 6, and/or 12-months, with some variation by center. Data captured via case report forms included medical/surgical history, number of anti-epileptic drugs (AEDs) tried, duration from epilepsy diagnosis to screening for this study, seizure count since last visit, concomitant medications, adverse events, radiographic findings, neuropsychological tests, and healthcare utilization variables including length-of-stay and level-of-care during hospitalization. RESULTS: Median age was 40 years (5-70 years). AEDs were kept constant throughout the 1-year course by most centers. At 6-month follow-up of all available consecutive subjects (ie, since 10/20/10) for whom data was available, 52% (20/39) at 6-months and 48% (14/29) at 12-months follow-up were seizure-free. However, for procedures performed after 7/1/12, at 6-month follow-up 63% (15/24), and at 12-months 69% (9/13) were seizure-free, suggesting improved outcome with experience. Similarly, 64% (9/14) for procedures performed after 1/1/13 were seizure-free at 6-months. Procedure-related adverse events recorded in all patients included headache (N = 10), visual field disturbance (N = 3), psychiatric disturbance (N = 3), hemorrhage (N = 2), and cellulitis (N = 1). Median length-of-stay was 1 day. Four patients underwent anterior temporal lobectomy for persistent seizures. CONCLUSION: SLAH appears to be a safe procedure and achieves seizure-freedom for a substantial proportion of patients with MTLE. Data support a procedural “learning curve,” plateauing at ∼65% seizure-free. Further prospective study, with greater numbers of subjects, could help elucidate and/or strengthen these findings.