Psoriasis is a chronic inflammatory disorder associated with increased cardiovascular mortality. Psoriasis affects high-density lipoprotein (HDL) composition, generating dysfunctional HDL particles. However, data regarding the impact of anti-psoriatic therapy on HDL composition and function are not available. HDL was isolated from 15 psoriatic patients at baseline and after effective topical and/or systemic anti-psoriatic therapy and from 15 age- and sex-matched healthy controls. HDL from psoriatic patients showed a significantly impaired capability to mobilize cholesterol from macrophages (6.4 vs. 8.0% [(3)H]-cholesterol efflux, P<0.001), low paraoxonase (350 vs. 217 μM/min/mg protein, P=0.011) and increased Lp-PLA2 activities (19.9 vs. 12.1 nM/min/mg protein, P=0.028). Of particular interest, the anti-psoriatic therapy significantly improved (i) serum lecithin-cholesterol acyltransferase activity and decreased total serum lipolytic activity but did not affect serum levels of HDL-cholesterol. Most importantly, these changes were associated with a significantly improved HDL-cholesterol efflux capability. Our results provide evidence that effective anti-psoriatic therapy recovers HDL composition and function, independent of serum HDL-cholesterol levels and support to the emerging concept that HDL function may be a better marker of cardiovascular risk than HDL-cholesterol levels.Journal of Investigative Dermatology accepted article preview online, 28 August 2013. doi:10.1038/jid.2013.359.