Background: Mitochondrial dysfunction can happen in any organ, and ocular symptom in mitochondrial disease is also important. However, there are few studies about patient with ophthalmoplegia in mitochondrial disease like Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO) or etc. Our aim is to evaluate the classification, diagnosis, and natural course of patients with ophthalmoplegia in mitochondrial disease. Method: We studied 21 patients with ophthalmoplegia among 372 patients with mitochondrial disease. But only 16 patients, except follow-up loss, were included in this study. They were divided into 3 groups (KSS, KSS-like, CPEO) by 3 criteria (onset age before 20, pigmentary retinopathy, cardiac involvement). Results: The male-to female ratio was about 1.3:1. Ptosis or retionopathy had over 80%. Patients with myopathy including extra-ocular muscle were 75%. Lactic acidosis (71%) and elevated serum creatine kinase level (47%) were noted. Half of the patients were normal in MRI study. Mitochondrial respiratory chain complex I defects in biochemical enzyme assay were most common (50%). Abnormal muscle pathologic finding in light microscopy or electron microscopy were each 50%. Mitochondrial DNA large deletion and point mutation in gene study were each 25% and 13%. Furthermore, we compared KSS & KSS-like patient group with CPEO patient group. There were statistically significant difference between 2 groups in pigmentary retinopathy, cardiac conduction disease, and mtDNA large deletion. Conclusions: In this study, mean age were older and mean follow-up duration was longer than other mitochondrial disease. KSS patients had gastro-intestinal symptoms unlike the existing definition of KSS and this could be other aspect of systemic involvement of KSS. Even though mtDNA large deletion was not always found in KSS, but that was an objective diagnosis for KSS. Therefore, examining gene study was worth to evaluate KSS.