General practitioners (GPs) should determine if their patients are taking inappropriate medications and reduce or halt them (deprescribe), but GPs who treat oldest old, multimorbid patients with polypharmacy are faced with hard decisions in response to complex conditions. To find out whether, how, and why Swiss GPs would deprescribe for these patients, we presented GPs with case-vignettes of a frail oldest-old patient, with and without a history of cardiovascular disease (CVD). In their responses to our online survey, we found Swiss GPs were willing to deprescribe cardiovascular preventive medication if the patient had no history of CVD. Their decisions were guided by risks and benefits of medications, patient quality of life and life expectancy, and the patient’s priorities. GPs tended to retain pain medication; if they were concerned about side-effects, they would reduce the dose or prescribe it as reserve medication. Next, we plan to compare our results to those from an ongoing survey in 31 other, mostly European countries. If we find GP prescription practices vary by country, we will try to find out why. Ultimately, we will support GPs by, for example, drafting deprescription guidelines tailored to primary care.