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Background: Atopic dermatitis (AD) in adults over 45 years of age (AD≥45) has been poorly studied. Objectives: To determine whether the AD phenotype varies according to the pattern of AD onset in AD≥45 patients and whether response to cyclosporine A (CsA) is influenced by age. Materials and Methods: This monocentric retrospective study was performed in a French university department of dermatology. We included 409 AD<45 patients (111 treated with CsA) and 124 AD≥45 patients (26 treated with CsA). Among AD≥45 patients, 20% were categorised into Subgroup 1 (persistence of AD since childhood), 52% into Subgroup 2 (recurrence of AD with a history of classic childhood AD), and 28% into Subgroup 3 (adult-onset AD). Results: Gender, associated atopic comorbidities, a family history of atopy, and AD severity were similar regarding the different patterns of AD onset in AD≥45 patients. Skin lesions predominated on the face and neck in AD≥45 patients with AD since childhood (30% in Subgroups 1 and 2) compared to those with adult-onset AD (14% in Subgroup 3). The efficacy of CsA was similar between groups AD≥45 and AD<45, but 28% of AD≥45 patients versus 20% of AD<45 patients had increased serum creatinine levels under CsA. Conclusion: No significant association seems to exist between the onset of AD and demographic or clinical characteristics in AD≥45 patients (except that head and neck involvement is rarer in adult-onset AD). Patient age does not influence response to CsA, but this drug appears to be less well tolerated in older patients.