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Background: Little is known about the longitudinal course of adult atopic dermatitis (AD) lesional severity and extent in clinical practice., Objective: To determine the longitudinal course of AD in clinical practice., Methods: A prospective, dermatology practice-based study was performed (n = 400). Patients were assessed at baseline and approximately 6, 12, 18, and 24 months by eczema area and severity index (EASI) and objective-scoring atopic dermatitis (objective-SCORAD). Multivariable repeated measures linear regression models were constructed to evaluate AD severity over time., Results: Overall, 36.2% and 18.2% of patients had moderate (6.0-22.9) or severe (23.0-72.0) EASI scores at any visit, respectively. Similarly, 29.0% and 26.4% of patients had moderate (24.0-37.9) or severe (38.0-83.0) objective-SCORAD scores at any visit, respectively. Among patients with baseline moderate (6.0-22.9) or severe (23.0-72.0) EASI scores, 25.0% and 18.6% continued to have moderate or severe scores at 1 or more follow-up visits, respectively. Similarly, among patients with baseline moderate (24.0-37.9) or severe (38.0-83.0) objective-SCORAD scores, 22.6% and 24.5% continued to have moderate or severe scores at 1 or more follow-up visits, respectively. In longitudinal regression models, EASI was significantly associated with body surface area (adjusted β [95% confidence interval]: 0.16 [0.09-0.23]) and edema/papulation (2.31 [0.19-4.43]). In addition, objective-SCORAD was significantly associated with body surface area (0.12 [0.04-0.21]), edema/papulation (4.69 [2.05-7.32]), and scratch (3.34 [0.45-6.24]) over time., Conclusion: AD lesional severity has a heterogeneous longitudinal course. Many patients had fluctuating lesional severity scores over time. A minority of patients had persistently moderate or severe lesions over time. Most patients with moderate-severe disease at baseline were unable to achieve persistent lesional clearance., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)