BackgroundGender-sensitive approaches to health communication aim to integrate gender perspectives at all levels of communication, as an individual’s biological sex and socially assigned gender identity have an impact on whether and how one acquires what type of health information. Due to the fast and low-cost opportunity to search for a wide range of information, the internet seems to be a particularly suitable place for gender-related health information about diseases of sex-specific organs and diseases where biological differences are associated with different health risks.ObjectiveThis study aims to inform gender-related information provision and acquisition in 2 ways. The first objective was to provide a theory-driven analysis of web-based health information–seeking behavior (HISB) regarding gender-related issues. Therefore, the Planned Risk Information Seeking Model (PRISM), which is one of the most integrative models of HISB, was adapted and applied. Second, we asked for gender-specific motivational determinants of gender-related web-based HISB comparing the predictors in the groups of women and men.MethodsData from a stratified web-based survey of the German population (N=3000) explained gender-related web-based HISB and influencing patterns comparing women and men. The applicability of PRISM to gender-related web-based HISB was tested using structural equation modeling and a multigroup comparison.ResultsThe results revealed PRISM as an effective framework for explaining gender-related web-based HISB. The model accounted for 28.8% of the variance in gender-related web-based HISB. Gender-related subjective norms provided the most crucial explanatory power, followed by perceived seeking control. The multigroup comparison revealed differences in the model’s explanatory power and the relevance of predictors of gender-related web-based HISB. The share of explained variances of web-based HISB is higher in men than in women. For men, norms were a more relevant promoting factor, whereas web-based HISB of women was more strongly associated with perceived seeking control.ConclusionsThe results are crucial for gender-sensitive targeting strategies and suggest gender-related health information interventions that address gender-related subjective norms. Furthermore, programs (eg, web-based learning units) should be developed and offered to improve individuals’ (perceived) abilities to perform web-based searches for health information, as those with higher control beliefs are more likely to access web-based information.