BackgroundMalaria still represents one of the most debilitating and deadly disease in the world; an estimated 229 million cases of malaria occurred globally in 2019 resulting in 409 000 deaths. The ongoing struggle for malaria elimination requires the scientific community to employ new methods. Gender-based medicine continues to acquire more importance in non-communicable as well as communicable diseases. It has been suggested that malaria has different impact on women and men due to both social and biological factors. A gender perspective is therefore important to understand how to eliminate malaria. MethodsThe enrolment of this study was conducted between June and October 2018 at the HopeXchange Medical Centre (HXC), located in the suburbs of Kumasi (Ghana). A sequential mixed-methods design comprising quantitative and qualitative methods was used. The quantitative methods consisted in the prospective assessment of malaria cases presented to hospital with malaria infection, along with a case-control investigation in the hospital catchment area. Whereas focus group discussions and in-depth interviews were employed as qualitative approaches. ResultsOne hundred-and-twenty-four individuals were diagnosed with malaria at HXC and enrolled. This study found a low ownership (40%) and use (19%) of insecticide-treated nets (ITNs) compared to the national data (57%). Most malaria cases were women (62%), who were less educated and had more external risk factors associated with infection. Our study reported a trend of preferring malaria self-medication at home. This was practiced mostly by men (43%) and more among cases (38%) than controls (21%). Many misconceptions and beliefs about malaria still exist in some Kumasi communities. ConclusionsThe mixed methods approach employed in this study allowed the identification of gender differences in risk factors for malaria infection. The study unexpectedly found a decreased ITN use and an increased self-medication preference among respondents. Our data suggest that women are more likely to be exposed to malaria infections than men, especially due to their prolonged exposure to mosquito bites during the most dangerous hours. Our study highlighted the need for future malaria control policies to be more focused on social and behavioral aspects, and not only concentrated on biological or clinical factors.