Syphilis is a chronic infectious disease with its prevalence being described since the 15 th century. Although its etiological agent and also the treatment measures are widely known, syphilis is still a great public health problem worldwide, mainly in countries with limited resources associated to low investments in health primary care. The aim of the present study was to analyze the trend and regional distribution of syphilis in Brazil between 2007 and 2017. This is an ecological study using secondary data from the Brazilian notification system. The Ministry of Health selected 100 municipalities which presented the worse outcomes related to syphilis from the 5,570 Brazilian municipalities as a target for a comprehensive project in order to tackle the prevalence of syphilis, called the "No Syphilis Project". These priority municipalities represent 57.7% of syphilis cases and about one third of the Brazilian population. They were compared with other 189 non-priority municipalities with more than 100 thousand inhabitants among the Brazilian regions (North, Northeast, Southeast, South and Center-West). Polynomial regression methods and Joinpoint analyses were used to analyze the trend, from which the Annual Average Percent Change (AACP) for each time period was calculated. There was a significant growth trend in all regions for the main three forms of syphilis (in pregnancy, congenital and acquired), especially in the South. The ratio between syphilis in pregnancy and congenital syphilis increased in both priority (AAPC: 8.54%; p<0.001) and non-priority municipalities (AAPC: 2.61%; p = 0.005), as well as in the regions, except the Center-West. High growth trends in syphilis prevalence were found in all municipalities, as well as all five regions between 2007 and 2017, showing that the challenge to reduce or even eliminate syphilis in Brazil is still difficult.