Introduction: There are limited studies on the epidemiology of syphilis in Malaysia. In this study we describe the clinical features and treatment outcomes of patients with syphilis attending a tertiary referral university hospital. Methods: We retrospectively reviewed the case records of patients with positive serology findings for syphilis in University Malaya Medical Center (UMMC) from January 2010 to December 2015. Serological positivity was defined as having a positive rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) with a confirmatory positive Treponema pallidum particle agglutination assay (TPPA). Treatment outcomes were divided into two, success or failure. Demographic and clinical characteristics associated with predictors of treatment failure were assessed using statistical package for the social science (SPSS). This study also included a neurosyphilis descriptive sub-study. Results: There were 637 patients identified with positive syphilis serology, but 258 patients were excluded as they did not meet the inclusion criteria. 379 patients were then taken for the demographic study; 14 patients (3.7%) were treated for neurosyphilis; 170 patients with complete data were included. In all 42/170 (24.7%) failed treatment, 12/170 (7.1%) had reinfection and 116/170 (68.2%) had treatment success. A final number of 158 patients were then taken and analyzed for predictors of treatment failure after excluding the 12 reinfection patients. Only low baseline RPR (<1:16) was found to be significant on multivariate logistic regression analysis (p value: 0.007, 95% CI: 1.42, 9.21). Conclusion: Most of the patients were HIV positive and from the MSM (Men who have sex with Men) population. Low baseline RPR titre is a predictor of treatment failure.