Introduction Mental health is marked by gender differences. We formed a multi-cohort consortium to perform GEnder-Sensitive Analyses of mental health trajectories and study their implications for prevention (GESA). GESA aims at (1) identifying gender differences regarding symptoms and trajectories of mental health over the lifespan; (2) determining gender differences regarding the prevalence, impact of risk and protective factors; and (3) determining effects of mental health on primary and secondary outcomes (eg, quality of life, healthcare behaviour and utilisation).Methods and analysis We plan to perform secondary analyses on three major, ongoing, population-based, longitudinal cohorts (Gutenberg Health-Study (GHS), Study of Health in Pomerania (SHIP), Cooperative Health Research in the Augsburg Region (KORA)) with data on mental and somatic symptoms, medical assessments and diagnoses in north-east, middle and southern Germany (n>40 000). Meta-analytic techniques (using DataSHIELD framework) will be used to combine aggregated data from these cohorts. This process will inform about heterogeneity of effects. Longitudinal regression models will estimate sex-specific trajectories and effects of risk and protective factors and secondary outcomes.Ethics and dissemination The cohorts were approved by the ethics committees of the Statutory Physician Board of Rhineland-Palatinate (837.020.07; GHS), the University of Greifswald (BB 39/08; SHIP) and the Bavarian Chamber of Physicians (06068; KORA). Together with stakeholders in medical care and medical training, findings will be translated and disseminated into gender-sensitive health promotion and prevention.