The aim is to highlight the influence of patients’ gender on Lyme borreliosis and especially erythema migrans (EM), focusing on exposure to tick bites, epidemiology, and the clinical picture. All studies were conducted in the county of Blekinge, located in southeastern Sweden. A prospective study was conducted in 235 individuals (women, n=110; men, n=125) engaged in recreational or occupational activities focusing on exposure to tick bites. A retrospective epidemiological study evaluating 123,495 electronic patients´ records (women, n=61,712; men, n=61,783) and a prospective clinical study including 118 patients (women, n=54; men, n=64) 18 years or older seeking care for EM > 5 cm in diameter with genospecies verified by polymerase chain reaction were conducted. Results: Women 40 years or older had a 48% higher risk than men 40 years or older and 42% higher risk than women younger than 40 years of attracting tick bites (0.0188 versus 0.0127 and 0.0188 versus 0.0132 tick bites respectively per hour). Additionally they had a 96% higher risk than men younger than 40 years of attracting tick bites (0.0188 versus 0.0096). The annual incidence rate of EM in women was 506 and in men 423 cases per 100,000 inhabitants (p<0.001). Significant differences in incidence rates occurred in those 40 years or older. Odds ratios for males infected with Borrelia afzelii developing nonannular EM were 0.09 (95% confidence interval [CI] 0.03 to 0.33) in comparison with females infected by Borrelia afzelii. Conclusions: Significant gender differences in the risk of contracting tick bites, incidence rates, and clinical picture of EM have been observed. Exposure to tick bites alone may not explain these observations and further studies need to be done to clarify the biologic, immunologic, and sociological mechanisms causing these differences.