Background Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. The disease affects all ages and both sexes but more prevalent among the sexually active age group of 15–49 years. The purpose of the current study was to determine the prevalence and factors associated with syphilis infection among outpatients 15–49 years in the Asikuma Odoben Brakwa District of Ghana where high levels of infection were earlier reported among antenatal women. Methods A descriptive cross-sectional study was carried out in 13 randomly selected health facilities. Blood samples were collected and tested for syphilis infection and a questionnaire administered to determine factors associated with the disease. Results A total 277 patients aged 15–49 years participated in the study. The overall prevalence of syphilis infection was 3.2% (9/277), with 5.7% (6/105) and 1.7% (3/172) among males and females respectively. Significant factors associated with syphilis infection included sub-district of residence, (χ 2 (4) = 31.20, p < 0.001) and history of coerced sexual intercourse (χ 2 (1) =7.49, p = 0.006). Conclusions The prevalence of syphilis infection was high among male patients who lived in rural areas. Having a history of coerced sexual intercourse was a strong predictor for syphilis infection. Access to sexually transmitted infection control interventions in rural communities including health education may help control the disease. Electronic supplementary material The online version of this article (10.1186/s12879-019-3967-6) contains supplementary material, which is available to authorized users.