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There is a lack of efficacious topical treatments for patients suffering from psoriatic nail disease (PND). We investigated the efficacy of Calcipotriol‐Betamethasone Dipropionate (Cal/BD) foam with and without ablative fractional laser (AFL) in patients with PND. A total of 144 nails from 11 patients were treated in a 24‐week long, open‐label, randomized, intra‐patient controlled proof‐of‐concept hybrid trial. In addition to daily Cal/BD foam application, half of each patient's psoriatic nails were randomized to receive optical coherence tomography (OCT)‐guided AFL treatment at baseline, 6‐, and 12‐week follow‐ups. In‐clinic assessment (N‐NAIL), patient‐reported outcomes (PROMs), and drug consumption were supplemented by remote evaluation of 15 subclinical OCT features, smartphone app‐based safety monitoring, and photo‐based assessment (NAPSI). After 24 weeks of Cal/BD foam treatment, patients achieved a significant improvement (p < 0.001) in both clinical (N‐NAIL −76%, NAPSI −68%) and subclinical (OCT −43%) PND severity as well as a 71% reduction in PROMs. AFL‐assisted Cal/BD treatment led to higher clinical (N‐NAIL −85%, NAPSI −78%) and OCT‐assessed (−46%) reduction of PND signs than Cal/BD alone (N‐NAIL −66%, NAPSI −58%, OCT −37%), but did not reach statistical significance. Smartphone app images documented adverse events and mild local skin reactions, particularly erythema (75%), laser‐induced swelling (28%), and crusting (27%). This hybrid trial demonstrated a reduction in clinical NAPSI and N‐NAIL scores, subclinical OCT features, and PROMs, suggesting that Cal/BD foam is a safe and efficacious treatment for PND. Larger trials are warranted to prove the clinical benefit of AFL pretreatment as a Cal/BD delivery enhancer. [ABSTRACT FROM AUTHOR]