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Background and aims In patients with psoriasis, the chronic exposure to systemic inflammation can result in coronary microvascular dysfunction (CMD). In this self-controlled, prospective pilot study, we investigated whether a long-term treatment with TNF-α inhibitors effective against skin symptoms also improves coronary flow reserve in psoriasis patients (CFR). Methods We prospectively studied 37 consecutive psoriasis patients (31 male; age, 37.7 ± 8.5 years) without cardiovascular disease, before and after anti-TNF-α treatment. CFR in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest and during adenosine infusion. CFR was the ratio of hyperemic to resting diastolic flow velocity. A CFR ≤ 2.5 was considered a marker of CMD. Psoriasis was assessed by Psoriasis Area and Severity Index (PASI). High sensitive C-reactive protein (hs-CRP) and serum TNF-α were assessed. Results Overall, CFR increased from 2.2 ± 0.7 to 3.02 ± 0.8 ( p < 0.0001) after TNF-α inhibitors therapy. In patients with CMD, CFR increased from 1.88 ± 0.3 to 2.74 ± 0.5 ( p < 0.0001). In patients with normal CFR, CFR increased from 3.0 ± 0.5 to 3.7 ± 0.9 ( p = 0.08). CFR improvement after TNF-α inhibitors treatment was correlated with hs-CRP and TNF-α reduction ( p = 0.004 and p = 0.02, respectively), but not with change in PASI ( p = 0.5). Conclusions The present study demonstrates that TNF-α inhibitors treatment ameliorates CMD in patients with established psoriasis not responding to long-term conventional therapy. These findings suggest that a therapy specifically targeted against inflammation is able to positively affect coronary microvascular function. [ABSTRACT FROM AUTHOR]