Background and Purpose—We systematically reviewed the literature on epidemiology, risk factors, presumed cause, clinical course, and outcome of perimesencephalic hemorrhage.Methods—PubMed, Embase, and the Cochrane Library were searched until March 2016. Quality assessment was done by 2 authors independently. Pooled prevalence ratios and pooled odds ratios with 95% confidence intervals were calculated for data extracted from case–control studies.Results—We included 208 papers. The incidence of perimesencephalic hemorrhage is ≈0.5 per 100.000 person-years, men are more often affected, and no risk factors were confirmed. Two decision analyses both found that a single, high-quality computed tomography angiography is the preferred diagnostic approach. Short-term complications, such as hydrocephalus or cranial nerve palsies, are rare, and usually transient, with the exception of acute symptomatic hydrocephalus necessitating treatment in 3% of patients. Lacunar infarcts in the brain stem were convincingly described in 4 patients only. Fatal rebleeding after installment of anticoagulation in the initial days after the hemorrhage was described in 1 patient. At long-term follow-up, death related to the hemorrhage has not been reported, disability is found in 0% to 6%, and neuropsychological sequelae are suggested.Conclusions—A single, high-quality computed tomography angiography is the preferred diagnostic strategy. Short-term complications are rare and often transient. Long-term outcome is excellent with respect to disability and death, but high-quality studies focused at neuropsychological sequelae are needed.