Objectives This study addresses the lack of empirical studies about the epidemic of syphilis among middle-aged female sex workers (FSWs). The objectives of this study were to investigate prevalence of syphilis, and its potential risk factors among middle-aged FSWs in China.

Design A cross-sectional study with respondent-driven sampling (RDS).

Setting A multisite study conducted at three Chinese cites (Nanning, Hefei, and Qingdao) with different levels of sexually transmitted diseases in 2014.

Participants 1245 middle-aged female sex workers who were over 35 years old (about 400 per study site).

Main outcome measures Unprotected commercial sex, and syphilis and HIV infection were biologically tested and measured.

Results The RDS-adjusted prevalence of active syphilis was 17.3% in Hefei, 9.9% in Qingdao, and 5.4% in Nanning. The RDS-adjusted prevalence of prevalent syphilis was between 6.8% and 33.6% in the three cities. The proportion of unprotected sex in the past 48 h verified by the prostate-specific antigen test (PSA) was between 27.8% and 42.4%. Multiple log-binomial regression analyses indicate that middle-aged FSWs who had 5 or more clients in the past week prior to interviews and engaged in unprotected sex were more likely to be active syphilitic cases. Middle-aged FSWs who had rural residency were less likely to be active syphilitic cases.

Conclusions In contrast with previous studies that reported low prevalence of syphilis and high prevalence of protected sex among FSWs in China, both the prevalence of syphilis and unprotected sex were high among middle-aged FSWs. Evidence-based intervention programmes should be developed and evaluated among this vulnerable population in China and other countries with similar settings.