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Zambia has a serious HIV epidemic and syphilis infection remains prevalent in the adult population. We investigated syphilis trends using national antenatal clinic (ANC) sentinel surveillance data in Zambia and compared the findings with population-based data.The analyses are based on ANC data from 22 sentinel sites from five survey rounds conducted between 1994 and 2008. The data comprised information from interviews and syphilis and HIV test results. The syphilis estimates for 2002 and 2008 were compared with data from the Demographic and Health Surveys 2001/2002 and 2007, which are nationally representative data, and also included syphilis testing and HIV.The overall syphilis prevalence dropped during the period 1994–2008 among both urban and rural women aged 15 to 49 years (9.8% to 2.8% and 7.5% to 3.2%, respectively). However, provincial variations were striking. The decline was steep irrespective of educational level, but among those with the highest level the decline started earlier and was steeper than among those with low education. The comparison with Zambia Demographic and Health Surveys 2001/2002 and 2007 findings also showed an overall reduction in syphilis prevalence among urban and rural men and women in the general population.The syphilis prevalence declined by 65% in urban and 59% in rural women. Provincial variations need to be further studied to better guide specific sexually transmitted infection prevention and control programmes in different geographical settings. The national ANC-based HIV and syphilis surveillance system provided good proxies of syphilis prevalence and trends.