Criteria have been developed to identify potentially inappropriate medications that can enhance adverse reactions, highly prevalent in older patient’s therapy. This study aimed to identify potentially inappropriate medications within the adverse drug reactions reported in the Portuguese pharmacovigilance system, characterizing the reports where inappropriate medications were identified. INFARMED, I.P. provided all adverse drug reactions reported from January to December 2019 in 65-year-old and older patients. Adverse drug reactions were characterized according to the System Organs Classes, seriousness, and medications with the Anatomical Therapeutical Classification. Potentially inappropriate medications were identified by applying the EU-(7)-PIM and the Beers criteria. A p value < 0.05 was considered statistically significant. From the 2337 reports considered for the analysis, PIMs were found in 12.8% of these, and 64.7% of all adverse reaction reports were classified as serious. Within the group of reports including at least one PIM, 71.4% were classified as serious, with hospitalization the most common criteria (35.1%). From the 3170 suspected medicines identified, 10.6% were classified as PIMs. Amiodarone was the most frequent PIM identified in the study (10.1%). Reports including at least one PIM were more associated with a higher number of ADRs (p = 0.025) reported in the same record, higher number of suspected medicines identified (p < 0.001), seriousness (p = 0.005), and hospitalization (p < 0.001). Potentially inappropriate medications are important enhancers of serious adverse drug reactions, increasing the likelihood of hospitalizations. This reinforces the importance of improving medication appropriateness in the older population.