Background: Essential tremor (ET), the most common movement disorder, often impairs patients’ ability to perform activities of daily living, mental health, and quality of life.Objectives: To assess comorbidities, psychiatric disorders, healthcare resource utilization (HCRU), and costs among patients with ET compared with patients without ET.Methods: This retrospective observational study was conducted using a large US administrative claims database. Patients with ET were identified during the study period (1/1/2017–12/31/2019). The earliest claim date with ET diagnosis was identified as the index date. An index date was assigned randomly for each non-ET patient. Patients had to be at least 22 years old and be enrolled in the health plan for at least 6 months before and at least 12 months after the index date. Patients with and those without ET were matched 1:1 on age, gender, payer type, and first 3 digits of their ZIP code. Comorbidities were assessed using data within 6 months prior to the index date. Psychiatric disorders, HCRU, and costs were examined using data within 12 months after the index date.Results: The mean (SD) age of ET patients (n = 5286) was 70.8 (11.8) years, 49.1% were female, and 82.9% were Medicare Advantage members. In the 12 months following the index date, 26.0% of patients had no insurance claims for ET-related pharmacotherapy or invasive therapies. Patients with ET had a higher number of comorbidities than non-ET patients (5.3 [3.2] vs 4.0 [3.3]); a higher prevalence of psychiatric disorders (depression: 25.6% vs 15.3%; adjusted odds ratio (AOR) [95% CI], 1.56 [1.41-1.73]; anxiety: 27.7% vs 15.5%, AOR: 1.78 [1.61-1.96]); and higher total healthcare costs: $17 560 [$39 972] vs $13 237 [$27 098], adjusted cost ratio [95% CI]: 1.11 [1.06-1.16]; all P<.0001.Discussion: Highly prevalent multiple comorbidities and psychiatric disorders should be considered in the context of clinical decision-making to optimize ET management.Conclusions: This study represents the largest observational study to report ET disease and economic burdens in a real-world setting. The data demonstrate increased comorbidity, mental health, and healthcare cost burdens among ET patients compared with matched non-ET patients. These findings underscore the need for innovative care for this complex population.