Background: Most patients with Lyme disease (LD) can be treated effectively with 2-4 weeks of antibiotics. The Infectious Disease Society of America guidelines do not currently recommend extended treatment even in patients with persistent symptoms. Methods: To estimate the incidence of extended use of antibiotics in patients evaluated for LD, we retrospectively analyzed claims from a nationwide US health insurance plan in 14 high-prevalence states over 2 periods: 2004-2006 and 2010-2012. Results: As measured by payer claims, the incidence of extended antibiotic therapy among patients evaluated for LD was higher in 2010-2012 (14.72 per 100 000 person-years; n = 684) than in 2004-2006 (9.94 per 100 000 person-years; n = 394) (P < .001). Among these patients, 48.8% were treated with ≥2 antibiotics in 2010-2012 and 29.9% in 2004-2006 (P < .001). In each study period, a distinct small group of providers (roughly 3%-4%) made the diagnosis in >20% of the patients who were evaluated for LD and prescribed extended antibiotic treatment. Conclusions: Insurance claims data suggest that the use of extended courses of antibiotics and multiple antibiotics in the treatment of LD has increased in recent years.