Background <p>Adverse drug reactions (ADR) associated with local anesthetics (LA) like lidocaine are often interpreted as allergy. This assumption leads to a&#xa0;large number of allergological investigations. There are numerous studies that investigate the frequency of type&#xa0;I allergies to LA, and they all agree that a&#xa0;real type&#xa0;I allergy as the culprit of ADR to LA is extraordinarily rare. Other mechanisms are more likely. Specifically, the unequal sex distribution of patients with ADR is rarely discussed and hardly any studies address this topic.</p> Aim <p>The aim of this paper is to examine sex disparities in ADR to LA. Differences in symptoms, causes and pathomechanisms between men and women are analyzed.</p> Methods <p>This study integrates our own clinical data with a&#xa0;comprehensive literature review. Our data are based on an analysis of 140 patients with suspected allergy to LA. Patient anamnesis, clinical data and skin test results performed with different LA are analyzed in relation to the sex. A&#xa0;PubMed search provides comparative data.</p> Results <p>Our data and literature research show that women are significantly more likely than men to present to allergy centers with suspected allergies to LA. True type&#xa0;I allergies are exceedingly rare in both sexes. Symptoms of ADR can be diverse and there is no pathognomonic symptom and not even a&#xa0;symptom complex that reliably indicates a&#xa0;real type&#xa0;I allergy. Pharmacophysical differences, such as different drug distribution and metabolism, and psychological differences in females could account for a&#xa0;part of the symptoms.</p> Conclusion <p>The reason for the unbalanced sex distribution is still unknown, but probably multifactoral. A&#xa0;research focus on this subject is needed to better understand gender specific aspects, in order to provide more efficient workup in allergological diagnostics.</p> Graphical Abstract <p></p>