Background: A Lyme disease (LD) diagnosis can be far from straightforward, particularly if erythema migrans does not develop or is not noticed. Extended courses of antibiotics for LD are not recommended, but their use is increasing. We sought to elucidate the patient patterns toward a diagnosis of LD, hypothesizing that a subset of patients ultimately receiving extended courses antibiotics may be symptomatic for an extended period before the first LD diagnosis. Methods: Claims submitted to a nationwide U.S. health insurance plan in 14 high-prevalence states were grouped into standardized diagnostic categories. The patterns of diagnostic categories over time were compared between patients evaluated for LD and given standard antibiotic therapy (PLDSA) and patients evaluated for LD and given extended antibiotic therapy (PLDEA) in 2011-2012. Results: The incidence of PLDSA was 40.45 (N = 3207) and that of PLDEA was 7.57 (N = 600) per 100,000 insured over 2011-2012. 50.3% of PLDEA were diagnosed in the nonsummer months. Seven diagnostic categories were associated with PLDEA. From 180 days before the first LD diagnosis, the risks of having claims associated with back problems (odds ratio [OR], 2.1; confidence interval [95% CI], 1.4-2.9; p < 0.001) and connective tissue disease (OR, 1.6; 95% CI, 1.1-2.3; p < 0.01) complaints were higher among PLDEA. From 90 days before the diagnosis, malaise and fatigue (OR, 1.7; 95% CI, 1.1-2.6; p < 0.05), other nervous system disorders (OR, 2.0; 95% CI, 1.3-3.1; p < 0.01), and nontraumatic joint disorder (OR, 1.4; 95% CI, 1.0-2.0; p < 0.05) were more likely found among PLDEA than PLDSA. From 30 days before the diagnosis, the risk for mental health (OR 1.6; 95% CI, 1.1-2.0; p < 0.01) and headache (OR 1.5; 95% CI, 1.1-2.0; p < 0.05) among PLDEA was elevated. Conclusions: Among patients evaluated for LD and ultimately receiving an extended course of antibiotics for LD, 15.8% of them were symptomatic and seeking care for several months before their first LD diagnosis.