Background/Objectives: The appropriateness of statin treatment in frail older adults is controversial because of insufficient evidence on its efficacy. The aim of this study was to assess the appropriateness of statin prescription at admission and discharge from hospital and the association of deprescription with one-year mortality in a cohort of older patients. Methods: Monocentric retrospective observational study of older (≥65 year) adults admitted to a Geriatric Unit. Patients underwent comprehensive geriatric assessment and prevalence of statin prescription at admission and discharge was recorded. Appropriateness of prescription was determined using the Medication Appropriateness Index (MAI), multidimensional frailty using the Multidimensional Prognostic Index (MPI). Mortality at 12 months was recorded. Results: Among 528 consecutively admitted patients, 112 (mean age 83.6 ± 6.2 years) were treated with statins and were included in the study. In addition, 87.5% of patients showed at least one inappropriate criterion for statin prescription at admission and 91.7% at discharge. Deprescription occurred in 46.4% of patients at discharge, particularly in those who were older and in MPI high mortality risk class. Mean MAI did not differ between admission and discharge in the whole study cohort, but it decreased in patients at highest mortality risk (from 3.2 ± 4.0 to 2.0 ± 1.2). In multivariate analysis, compared with patients who continued statins after discharge, those who were deprescribed did not show increased one-year mortality risk. Conclusions: Inappropriate statin prescription is common at hospital admission in frail older patients and deprescription does not affect one-year residual survival. Therefore, rigorous assessment of mortality risk and medication appropriateness should be encouraged.