The aim of the study was to identify risk-factors associated with hypersensitivity to local anesthetic drugs in an ethnically homogenous population. Allergy to anesthetic agents were evaluated by skin tests and venous blood tests for presence of allergen-specific immunoglobulins type E (IgE) by Enzyme-linked Immunoassay (ELISA). The skin tests were performed for the following local anesthetic groups: lidocaine, mepivacaine, articaine. HLA/KIR typing was performed by PCR using sequence-specific oligonucleotide probes (SSOP). 450 patients have been included in the study with age range between 4 and 79 years. Special questionnaire was used to collect demographic, family history and clinical data. By statistical analysis, the allergic status to anesthetic agent was associated with the presence of allergy to the different types of allergens among patients' mothers or sibships, presence of drug allergy, presence of food allergy in addition to the drug allergy among patients, presence of current or recent infectious diseases and specific HLA/KIR profiles (specifically HLAC1C1; KIR2DL2/2DL2; KIR2DL3/2DL3). Both genetic (family history, immunogentic profiles) and acquired (presence of recent or current infections) are associated with the development of hypersensitivity to local anesthetic agents. The obtained data can contribute to the clarification of immunogenetic mechanisms of development of drug-related allergies.