Objective To investigate the clinical features of neurosyphilis patients with ataxia as the primary manifestation. Methods A total of nine cases of neurosyphilis (neurosyphilis group) and nineteen cases of cerebral infarction (cerebral infarction group), both with ataxia as the primary manifestation, were enrolled. The clinical manifestations, cerebrospinal fluid (CSF) and serum test results for syphilis, electroencephalogram (EEG), and magnetic resonance imaging (MRI) results were retrospectively analyzed. The patients with neurosyphilis were treated with penicillin or ceftriaxone, and their CSF tests results for syphilis were compared before and after treatment. The quantitative ataxia test results were compared between the neurosyphilis group and cerebral infarction group. Results Ataxia involved both lower extremities in most patients and unilateral extremities or both upper extremities in a few patients. In the static posture and gait analysis, the patients in the neurosyphilis group showed poor standing ability with eyes open and obvious body shaking with eyes open and closed. In the limb movement coordination tests, the patients in the cerebral infarction group showed poor performance in the heel-knee-tibia test with uncoordinated movements and intentional tremor, the finger-nose test, drawing Archimedes spiral, and overall coordination of limb movements. All the patients in the neurosyphilis group showed positive results in the Treponema pallidum particle agglutination test, toluidine red unheated serum test, and Venereal Diseases Research Laboratory test, and the titer began to decrease gradually after treatment. Head MRI mainly showed acute cerebral infarction in the basal ganglia, multiple old infarcts in the brain, widening of the cerebral sulci, fissures, and cisterns, ventricular enlargement, and hippocampal atrophy in the temporal lobe. EEG showed moderate to severe abnormalities. The CSF leukocyte count was higher than the normal value in all the patients, and eight patients showed an increase in CSF protein content. Conclusions For patients with ataxia and featuring mental disorders, cognitive impairment, involvement of both upper or lower extremities or unilateral extremities, and poor performance in static posture and gait, the possibility of neurosyphilis needs to be considered.