Background: Adverse Drug Reactions (ADRs) are a significant public concern because of their impact on healthcare systems. Spontaneous reporting of ADRs is crucial for monitoring drug safety and recognizing possible risk factors. The objective of this study was to characterize ADR reports from the Allergy and Clinical Immunology Unit of the G. Martino University Hospital, Messina, Italy. Methods: A retrospective analysis was conducted, including all ADRs spontaneously reported from patients attending the clinic because of at least one previous ADR, from June 2022 to June 2024. Results: A total of 388 reports were collected, mainly from females (71.1%) and adult patients (84.3%). ADRs were mostly immediate, from antibiotics and anti-inflammatory drugs (61.5%), with a high prevalence of cutaneous and respiratory disorders. Delayed reactions were mostly from endocrine therapies, vaccines, and antiepileptics. Anaphylactic shock was present only in 13 ADR reports (3.35%). A higher risk of developing serious ADRs was found in elderly patients aged ≥65 years (p = 0.012). An original finding was that a positive history of allergies (p = 0.023) and past medical history of ADRs (p = 0.045) were negatively correlated to the occurrence of a serious ADR, probably because patients had been previously followed in an allergy setting and alerted about ADRs. Conclusions: This study underlines the role of ADR follow-up in allergy settings to identify preventable traits and related risk factors; appropriate ADR reporting and collaboration between allergists and pharmacovigilance centers can be a winning strategy for ADR prevention.