Background <p>Drug exposure is one of the potential mechanisms implicated in the onset or exacerbation of psoriasis. To date, several cardiovascular agents have been implicated. Sacubitril/valsartan (SV) has been widely used in the treatment of hypertension and heart failure (HF). Its common adverse reactions include angioedema, hypotension, renal impairment, and hyperkalemia. However, SV may cause psoriasis, which needs clinical attention.</p> Case presentation <p>This report describes a case of a middle-aged male patient who developed psoriasis following SV therapy. The rashes presented as well-demarcated red or violaceous plaques with noticeable scaling. After being diagnosed with psoriasis, he was started on topical clobetasol propionate ointment, and SV was discontinued and replaced with ramipril for blood pressure control. During follow-up, the skin lesions showed marked improvement. However, the patient developed similar cutaneous manifestations again when SV was re-administered. He had previously developed psoriasis while using nifedipine, but transitioned to olmesartan and subsequently improved significantly with topical medication. Sacubitril enhances the effect of natriuretic peptides, which may be accompanied by a compensatory increase in angiotensin Ⅱ (Ang Ⅱ) levels, possibly contributing to the psoriasis.</p> Conclusion <p>To the best of our knowledge, this is the first reported case worldwide of psoriasis potentially associated with SV, and the underlying mechanism appears likely to be related to sacubitril. It serves as a caution for clinicians prescribing SV, particularly in patients with a history of psoriasis or positivity for the HLA-Cw*0602 allele. Further studies are warranted to confirm the mechanism by which sacubitril induces psoriasis.</p>