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Background Neurosyphilis is one of the most feared complications of syphilis. The question of how to identify patients at higher risk in order for timely intervention whilst avoiding unnecessary lumbar puncture remains. Methods Between August 2009 and March 2013, a total of 834 HIV-negative patients with primary, secondary or latent syphilis were recruited. Venous blood and cerebrospinal fluid specimens were collected for diagnoses of syphilis and/or neurosyphilis and information of socio-demographic and behavioral characteristics was collected by interviewing with a questionnaire. Results The prevalence of neurosyphilis differed among patients with primary (7.1%), secondary (23.8%) and latent (26.6%) syphilis. Neurosyphilis was more likely in male patients (1.52-fold). Compared with patients aged <30 years, those aged 45-59 years and ≥60 years old had a 2.51-fold and 4.98-fold risk of neurosyphilis respectively. Male gender and age ≥45 years were consistently associated with neurosyphilis both in secondary and latent stage. There was a 2.68-fold, 2.55-fold and 3.67-fold increased risk of neurosyphilis when the serum RPR titer was 1:32, 1:64 and ≥1:128 compared to that of ≤1:16. ). Conclusions Male gender and age 45years are both correlated risk factors for neurosyphilis in HIV-negative patients with primary, secondary and latent syphilis. [ABSTRACT FROM AUTHOR]