Background. The length of antibiotic therapy and long-term outcomes in patients with early Lyme disease are incompletely described. We report the long-term clinical outcomes of patients with early localized and early disseminated Lyme disease based on the duration of antibiotic therapy prescribed. Methods. A retrospective cohort study and follow-up survey of patients diagnosed as having early localized and early disseminated Lyme disease from 1 January 2000 through 31 December 2004 was conducted in a Lyme disease-hyperendemic area. Results. Six hundred seven patients met the study inclusion criteria. Most patients (93%) were treated with doxycycline for treatment durations Of ≤10 days, 11-15 days, or ≥16 days in 17%, 33%, and 47% of doxycyclinetreated patients, respectively. Treatment failure criteria, defined before performing the study, were met in only 6 patients (1%). Although these 6 patients met a priori treatment failure criteria, 4 of these patients' clinical details suggested reinfection, 1 was treated with an inappropriate antibiotic, and 1 developed facial palsy early in therapy. Reinfection developed in 4% of patients. The 2-year treatment failure-free survival rates of patients treated with antibiotics for ≤10 days, 11-15 days, or ≥16 days were 99.0%, 98.9%, and 99.2%, respectively. Patients treated with antibiotics for ≥ 16 days had lower 36-item Short-Form Health Survey social functioning scores on the followup survey. No other differences were found in follow-up clinical status or 36-item Short-Form Health Survey scores by duration of antibiotic treatment. Conclusions. Patients treated for ≤10 days with antibiotic therapy for early Lyme disease have long-term outcomes similar to those of patients treated with longer courses. Treatment failure after appropriately targeted short-course therapy, if it occurs, is exceedingly rare.