Objective To explore positive screening rate of syphilis in the blood donors in Wenzhou, analyze its epidemiological characteristics and provide scientific basis for its prevention and control. Methods ELISA was used to detect the syphilis antibodies in the blood samples from voluntary donors in Wenzhou from 2016 to 2018. The detection and epidemiological characteristics of syphilis in the blood donors were analyzed. Results Totally 286 322 valid blood donation samples were received in Wenzhou from 2016 to 2018, of which 1 011 were positive in the primary screening of syphilis and the positive rate was 0.35%. There was lack of significance between the male (0.35%) and the female (0.36%) regarding the prevalence of syphilis (P>0.05). The positive rates of different age groups were significantly different. Results from pairwise comparison suggested that the positive rate of syphilis in the 31-45 years old group (0.40%) was significantly higher than that in the 18-30 years old group (0.33%) and the 46-60 years old group (0.31%). There were significant differences among different occupation groups and pairwise comparisons suggested: others (0.62%)>businessmen/the self-employed (0.38%)>teachers/cadres (0.16%)>students (0.09%), (P<0.001). There were significant differences among different education groups and pairwise comparisons suggested: junior high school and below (0.53%)>senior high School / technical secondary school (0.37%)>junior college and above (0.24%), (P<0.001). There was lack of significance among different blood types, different blood collection sites regarding the prevalence of syphilis (P>0.05). Conclusion According to the characteristics of syphilis in Wenzhou, the key prevention and control measures should be taken for the female, low age group, high age group, other occupations, businessmen/selfemployed, and low education population, so as to further reduce the incidence of syphilis among the population.