<p>Background: Polypharmacy increases the risk of adverse drug reactions due to the combinatorial effects of multiple drugs. This problem is associated with an aging population and increasing demand for drug therapies. We aimed to develop a “medication questionnaire” to prevent polypharmacy.</p><p>Methods: We created a “prototype medication questionnaire” after collecting insights from six national centers in Japan. We disseminated this questionnaire to pharmacists from September 1 to November 30, 2021, to collect information on drugs used by inpatients. We compiled the responses to create a broadly applicable “medication questionnaire.”</p><p>Results: Of 1,467 patients aged 50.7 ± 27.6 years taking 7.3 ± 4.8 medications, 43.8% (643/1,467) were using 1.6 ± 1.6 potentially inappropriate medications (PIMs). Geriatric syndrome and adverse drug events were present in 67.0% (588/878) of patients and included lightheadedness/falls (29.6%, 260/878) and anorexia (27.1%, 238/878). Adverse effects were higher among older adults (76.0%, 447/588, p < 0.01). We improved the “medication questionnaire” by changing the self-answer format; it is now available for open access (https://www.ncgg.go.jp/hospital/news/20230829-1.html).</p><p>Conclusions: We confirmed the possibility of readily identifying polypharmacy-associated problems, including geriatric syndrome and adverse drug events, and developed a “medication questionnaire” to prevent polypharmacy. When used in conjunction with the publicly available list of PIMs, we can identify drugs that should be considered for dose reduction and facilitate the optimization of prescribed regimens. We intend to use the results of this study as a reference to resolve polypharmacy-related issues and perform safe and appropriate pharmaceutical interventions.</p>