Older patients are vulnerable to adverse drug events due to comorbidities and polypharmacy. This cross-sectional study from Spain reviewed prescriptions for 593 older adults aged 65-75 years with multiple comorbidities and documented polypharmacy to estimate the prevalence of potentially inappropriate prescribing using the STOPP and Beers Criteria. Potentially inappropriate prescribing was detected in over half of patients. The most frequently detected inappropriate prescriptions were for prolonged use of benzodiazepines (36% of patients) and prolonged use of proton pump inhibitors (45% of patients). Multiple risk factors associated with potentially inappropriate prescribing were identified, including polypharmacy and use of central nervous system drugs.