Aim Polypharmacy is a highly prevalent geriatric syndrome, and hospitalizations can worsen it. The aim of the present study was to analyze the influence of hospitalization on polypharmacy and indicators of quality of prescribing, and their possible association with health outcomes. Methods A retrospective study of 200 patients discharged from an acute geriatric unit was carried out. Indicators of quality of prescription were registered at admission and discharge: polypharmacy defined as ≥5 medications, hyperpolypharmacy (≥10), potentially inappropriate prescribing by Beers and Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria, potentially prescribing omissions by Screening Tool to Alert doctors to the Right Treatment (START) criteria, drug interactions and anticholinergic burden measured with the Anticholinergic Risk Scale. Mortality, emergency room visits and hospital admissions occurring during 6 months after discharge were also registered. Results The total number of drugs increased at discharge (9.1 vs 10.1, P < 0.001), without increasing chronic medications (8.5 vs 8.3, P = 0.699). No significant variations were observed in the prevalence of polypharmacy (86.5% vs 82.2%), potentially inappropriate prescribing (68.5% vs 71.5%), potential prescribing omissions (58% vs 58%) or drug interactions (82.5% vs 83.5%). Patients with anticholinergic drugs tended to increase, not reaching statistical significance (39.5% vs 44.5%; P = 0.064). Polypharmacy was associated with emergency room visits (OR 2.62, 95% CI 1.07–6.40; P = 0.034), and hyperpolypharmacy with hospitalizations (OR 2.49, 95% CI 1.25–4.93; P = 0.009). Conclusions After hospitalization in an acute geriatric unit, the prevalence of polypharmacy, potentially inappropriate prescribing, potential prescribing omissions, interactions or anticholinergic drugs is still very high. Polypharmacy is a risk factor for hospitalization and emergency room visits. Measuring indicators of quality of prescription might be useful to design interventions to optimize pharmacotherapy and improve health outcomes in elderly acute patients. Geriatr Gerontol Int 2017; ••: ••–••.