The validity of self-reported medication use in epidemiological studies is an important issue in healthcare research. Here we investigated factors influencing self-reported medication use for multiple diagnoses in the seventh wave of the Survey of Health Aging and Retirement in Europe (SHARE) dataset in n = 77,261 participants (ages: mean = 68.47, standard deviation = 10.03 years). The influence of mental, physical, and sociodemographic parameters on medication self-report was analyzed with logistic regressions and mediation models. Depression, memory function, and polypharmacy influenced the self-report of medication use in distinct disorders to varying degrees. In addition, sociodemographic factors, knowledge about diagnosis, the presence of several chronic illnesses, and restrictions of daily instrumental activities explained the largest proportion of variance. In the mediation model, polypharmacy had an indirect effect via depression and memory on self-reported medication use. Factors influencing medication self-report vary between different diagnoses, highlighting the complexity of medication knowledge. Therefore, it is essential to assess the individual parameters and their effect on medication behavior. Relying solely on medication self-reports is insufficient, as there is no way to gage their reliability. Thus, self-reported medication intake should be used with caution to indicate the actual medication knowledge and use.