Background <p>Falls are a leading cause of hospitalisation among older adults, with substantial impacts on quality of life and healthcare costs. Fall-risk-increasing drugs represent an important risk factor.</p> Objective <p>This study aimed to evaluate the association between fall-risk-increasing drug use and the risk of fall-related hospitalisation.</p> Methods <p>A nested case-control study was conducted using administrative healthcare data from a sample of Italian community-dwelling older adults. Cases included individuals aged ≥65 years hospitalised for fall-related injuries in 2018, matched 1:1 by sex and age with controls who had no fall-related injuries. Fall-risk-increasing drug exposure was assessed by drug class, duration and recency of use. Adjusted odds ratios (aORs) were estimated using logistic regression, controlling for polypharmacy and comorbidities.</p> Results <p>Among 16,118 cases and 16,118 controls (68.77% female, mean age 79.76 years), cases showed a higher prevalence of polypharmacy (five to nine drugs: 42.03 vs 37.16%; ten or more drugs: 7.02 vs 5.44%; <i>p</i> &lt; 0.0001) and multimorbidity (three or more diseases: 6.42 vs 2.82%; <i>p</i> &lt; 0.0001). Fall-risk-increasing drug use was higher in cases (37.70 vs 26.49%, <i>p</i> &lt; 0.0001), with a 51% increased risk of fall-related hospitalisation (aOR 1.51, 95% confidence interval [CI] 1.44–1.59). Opioids (aOR 1.40, 95% CI 1.31–1.50) and antidepressants (aOR 1.45, 95% CI 1.36–1.54) were associated with the highest risk. Prolonged fall-risk-increasing drug exposure (&gt;9 months; aOR 1.69, 95% CI 1.57–1.83) and current exposure (within 30 days before hospitalisation; aOR 1.78, 95% CI 1.68–1.89) showed higher odds.</p> Conclusions <p>Fall-risk-increasing drug use was associated with a higher risk of fall-related hospitalisations in older adults. These findings support the importance of optimising prescribing and managing polypharmacy as potential strategies to improve patient safety and reduce the healthcare burden.</p>