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BackgroundGPs are confronted with therapeutic dilemmas in treating patients with multimorbidity and/or polypharmacy when unfavourable medication risk–benefit ratios (RBRs) conflict with patients’ demands.AimTo understand GPs’ attitudes about prescribing and/or deprescribing medicines for patients with multimorbidity and/or polypharmacy, and factors associated with their decisions.Design and settingCross-sectional survey in 2016 among a national panel of 1266 randomly selected GPs in private practice in France.MethodGPs’ opinions and attitudes were explored using a standardised questionnaire including a case vignette about a female treated for multiple somatic diseases, sleeping disorders, and chronic pain. Participants were randomly assigned one of eight versions of this case vignette, varying by patient age, socioprofessional status, and stroke history. Backward selection was used to identify factors associated with GPs’ decisions about drugs they considered inappropriate.ResultsNearly all (91.4%) responders felt comfortable or fairly comfortable deprescribing inappropriate medications, but only 34.7% decided to do so often or very often. In the clinical vignette, most GPs chose to discontinue symptomatic medications (for example, benzodiazepine, paracetamol/tramadol) because of unfavourable RBRs. When patients asked for ketoprofen for persistent sciatica, 94.1% considered this prescription risky, but 25.6% would prescribe it. They were less likely to prescribe it to older patients (adjusted odds ratio [AOR] 0.48, 95% confidence interval [CI] = 0.36 to 0.63), or those with a stroke history (AOR 0.55, 95% CI = 0.42 to 0.72).ConclusionIn therapeutic dilemmas, some GPs choose to prioritise patients’ requests over iatrogenic risks. GPs need pragmatic implementation tools for handling therapeutic dilemmas, and to improve their skills in medication management and patient engagement in such situations.