To summarize and analyze clinical and imaging data of three patients with hypertrophic olivary degeneration (HOD) and to systematically analyze the previous reported cases of HOD secondary to brainstem hemorrhage. Methods: The clinical features of 3 patients diagnosed with HOD were described. Furthermore, previous published cases of HOD secondary to brainstem hemorrhage were searched in PUBMED and Embase and retrospectively analyzed. Results: The average age of the 3 patients was 57.3 years. The symptoms of HOD were detected 4, 3, and 4 months after the primary neurological events respectively. The main clinical presentations included palatal myoclonus, nystagmus, head tremor, and ataxia. The primary lesions were all located in the pons. MRI disclosed enlarged inferior olivary nucleus (ION) and hyperintensity on T2-weighted images. All patients responded poorly to drug treatments. A total of 39 previous reported cases were included in the study. The mean age was 50.7 years for 25 (65.9%) males and 14 (34.1%) females. HOD occurred secondary to hemorrhage from cavernous hemangioma in 16 (41.0% ) cases and primary brainstem hemorrhage in 23 (59.0%) cases. The clinical symptoms of HOD were detected a median of 6 months (range, 3 months～15 years) after the primary neurological insult. The most frequent clinical manifestations were palatine myoclonus (38.5%), limb or head tremors (33.3%), and nystagmus (30.8%). Treatments included pharmacotherapy and surgery. Symptoms in 6/13 (46.2% ) cases improved after medication, and marked improvement was observed in all 3 patients who underwent surgical treatment. Conclusion: The diagnosis of HOD mainly depends on MRI and typical clinical manifestations, whereas the clinical features of HOD vary greatly among cases. Unilateral ION involvement and Holmes tremor is more frequently detected in HOD secondary to brainstem hemorrhage, and the effect of medical treatment is overall limited.