Over the last few years, the Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) criteria have been increasingly used to evaluate the prevalence of inappropriate prescribing. However, very few studies have evaluated the link between these criteria and clinical outcomes. The objectives of this study were to evaluate the prevalence of inappropriate prescribing according to STOPP and START in a population of frail elderly persons admitted acutely to hospital; to evaluate whether these inappropriate prescribing events contributed to hospital admissions; and to identify determinants of hospital admissions potentially related to inappropriate prescribing. This was a cross-sectional study including all frail older patients admitted to a 975-bed teaching hospital over a 12-month period. A pharmacist and a geriatrician independently detected events of prescribing of potentially inappropriate medication (PIM) and potential prescribing omission (PPO), using the STOPP and START criteria, respectively, in all patients included in the study. They determined whether the inappropriate prescribing event was the main cause or a contributory cause of hospital admission. Demographic, clinical and geriatric clinical syndromes (i.e. cognitive impairment, falls) were evaluated as potential determinants of hospital admissions related to inappropriate prescribing, using multivariate methods (i.e. logistic regression and a classification tree). 302 frail older persons (median age 84 years) were included in the study. PIMs (prevalence 48%) mainly involved overuse and/or misuse of benzodiazepines, aspirin and opiates. PPOs (prevalence 63%) were mainly related to underuse of calcium and vitamin D supplementation, aspirin and statins. Overall, inappropriate prescribing according to STOPP (54 PIMs) and/or START (38 PPOs) led or contributed to hospital admission in 82 persons (27%). The multivariate analyses indicated a relation between PIM-related admissions and a history of previous falls (p < 0.001), while the PPO-related admissions were associated with a history of osteoporotic fracture (p < 0.001) and atrial fibrillation (p = 0.004). Using the STOPP and START criteria, it was found that inappropriate prescribing events (both PIMs and PPOs) were frequent and were associated with a substantial number of acute hospital admissions in frail older persons. Fall-induced osteoporotic fracture was the most important cause of hospital admission related to inappropriate prescribing and should be a priority for pharmacological optimization approaches.