Office workers often report so-called sick building syndrome (SBS) symptoms affecting the skin, mucous membranes and nervous system. The recurring higher prevalence of SBS in women was investigated using questionnaire and ergonomic data from the German ProKlimA-Project. The hypothesis that working conditions and job characteristics for women are inferior to those of men was tested for groups of risk factors. Finally, gender-specific multiple logistic regression models were compared. It was found that 44.3% of women (n = 888) and 26.2% of men (n = 576) suffer SBS with significant differences between men and women for many variables. Considering sub-groups--supposing the same circumstances in psycho-social and work-related conditions--gender-specific SBS prevalence rates differ as for the whole sample, e.g. 35.9% of women with the most favourable job characteristic suffer SBS (men: 19.4%), 53.0% of women with the most unfavourable job characteristic suffer SBS (men: 33.3%). These results show that women suffer more SBS than men independent of personal, most work-related and building factors. Multiple logistic models define self-reported acute illness, job satisfaction, software quality and job characteristics as significant gender-independent risk factors. Number of persons/room, self-reported allergy and smoking are characteristic female risk factors. Age is a significant risk factor only in men.