Antihistamines for systemic use reduce or block the activity of histamine by competitive binding to the H1 receptor. They are the most commonly used in treating type I hypersensitivity reactions. The purpose of this thesis is to analyze the suspected adverse reactions of antihistamines for systemic use (ATK R06) reported to the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) in the period from 1 January 2015 to 31 December 2017. The data were analysed with regard to age and gender of a patient, type, seriousness, expectedness, outcome, distribution to System organ class (SOC) and reporter of the adverse reactions of antihistamines for systemic use including comparison with the total number of the reported adverse reactions to medicinal products. There were 161 reports of suspected adverse reactions in the analyzed period and the highest number was received from doctors and pharmacists for female patients and age group from 18 to 44 years. Of the 372 identified adverse reactions of antihistamines for systemic use, most have been reported for the System organ class (SOC) General disorders and administration site conditions, SOC Nervous system disorders and SOC Injury, poisoning and procedural complications. Somnolence and headache were the most common adverse reactions. 26,1% of adverse reactions of antihistamines for systemic use were evaluated as serious. Most of them were suicidal attempts and intentionally overdose with loratadine or desloratadine. The highest number of unexpected adverse reactions were reported for loratadine, desloratadine and fexofenadine. During analyzed period, the safety signal of antihistamines for systemic use (ATK R06) was not detected. The results from this study are in accordance with the previously recorded data from european (EudraVigilance) and the worldwide (VigiAccess) base of adverse reactions. According to the databases pharmacists are frequent reporters of adverse reactions due to the high number of nonprescription medicinal products which are present on the market. Although the number of suspected adverse reactions to antihistamines, as well as other medicinal products, is growing year after year, additional efforts are needed to raise awareness of the importance of spontaneous reporting. Therefore HALMED's work, as well as work of other agencies in the world, is of crucial importance for the development to safer use of medicinal products and the prevention of adverse reactions. The development of antihistamines for systemic use will increase the efficiency of their application for a specific indication and reduce the number of adverse reactions.