Background: We evaluate long-term post-operative hippocampal volume (HV) on non-epileptic hippocampus using MR volumetry as well as the neuropsychological outcome in patients with surgery for unilateral mesial temporal lobe epilepsy (MTLE) and achieved seizure-freedom. Methods: We studied 1.5-Tesla MRI before and after epilepsy surgery in 24 patients with MTLE. Serial MRI studies were scheduled at 4 post-operative consecutive periods; 6m-1y; 1-2y; 2-3y; 3-5y. We compared neuropsychological outcomes for memory and estimated IQ at the same periods with serial MRI up to 3 years. Results: The pre-operative non-epileptic HV was significantly smaller than HV in age-matched controls (n=14) (p<0.05). The HV became progressively atrophic after the surgery (p<0.05), correlating with the age at surgery (p<0.05) and pre-operative larger non-epileptic HV (p<0.05), but not with seizure duration. In 14 patients with non-dominant MTLE, the smaller dominant HV at 2-3y period correlated with decline of verbal memory (p<0.05). Conclusions: Post-operative progression of non-epileptic hippocampal atrophy was found with significantly more pronounce in patients with older age at surgery and larger pre-operative non-epileptic hippocampus. After the epileptogenic hippocampus is resected, the remaining hippocampus alone might exhaust to maintain the memory, especially in elders.