The objective of the study was to identify clinical and epidemiological characteristics of patients with infectious syphilis who presented with a high rapid plasma reagin (RPR) titre (≥1: 512) during the year of 2009 at the Miami Dade County Health Department (MDCHD) STD clinic. Potential cases were identified by a search in the electronic database. Among 519 individuals identified with reactive RPR, 190 individuals met criteria for infectious syphilis and 32 of them had at least one RPR titre of ≥1: 512. We found that the majority of individuals with high RPR were men who have sex with men (82%), from ethnic minorities (91%), and HIV infected (75%) but only 3 of them were on antiretroviral therapy. Overall, 50% of these patients with very high RPR titres were symptomatic, and the most common symptom was skin rash (93%).