Objective To investigate the clinical characteristics of neurosyphilis presenting clinically with cerebral infarction and study its treatment and prognosis. Methods A retrospective analysis was conducted in 41 patients with neurosyphilis who presented clinically with cerebral infarction. The clinical manifestations, neurological deficit scores, activity of daily life (ADL) scores, mental scale scores, and laboratory and imaging examination results of the patients were analyzed. Results Of the 41 patients, 23 exhibited reduced intelligence, 30 had limb paralysis, 8 had limb numbness, 2 complained of dizziness, and 1 experienced epileptic attacks. Head magnetic resonance imaging (MRI) revealed the presence of brain atrophy and multiple infarction foei without obvious space-occupying effect of cerebral edema in these patients. All the patients showed positive results of serum and cerebrospinal fluid Treponema pallidum hemagglutination assay (TPHA). After treatment with high-dose penicillin, 95.1% of the patients had improvements of the clinical symptoms. Conclusion The diverse clinical manifestations of neurosyphilis often result in misdiagnosis of the disease. Patients with neurosyphilis show multiple cerebral infarction foci and cerebral atrophy without obvious space-occupying effect on MRI. Penicillin can be an effective treatment in such cases, which generally have low rate of negative TPHA within 3 months. Such patients have more favorable clinical outcomes than those with common cerebral infarction, but poor prognosis is indicated in cases with concurrent extensive cerebral infarction.