Epidermal thickness (ET) has been suggested as a surrogate measure of psoriasis severity. Optical coherence tomography (OCT) is a recent imaging technology that provides real-time skin images to a depth of 1.8 mm with a micrometre resolution. OCT may provide an accurate in vivo measure of ET. It is, therefore, speculated that OCT may be used in the assessment of psoriasis vulgaris. A total of 23 patients with psoriasis vulgaris were systematically evaluated by OCT imaging and skin biopsy during treatment. Biopsies were graded for disease severity, and additional evaluation was done by the physician via psoriasis area and severity index (PASI) score, and by the patient through measures such as self-administered PASI, psoriasis life stress inventory index and dermatology life quality index. ET was calculated from OCT images. In comparison to normal skin, psoriasis appeared with a more irregular surface with a stronger entrance signal, a serrated dermo-epidermal junction was found and a less signal intensity in the dermis as shown in OCT images. ET measured in untreated plaques was thicker reflecting epidermal hyperproliferation and inflammation. The changes were significantly correlated with the biopsy grading (r (2) = 0.41, p = 0.001) and ET significantly decreased with treatment (p = 0.0001). ET correlated significantly with self-reported measures of disease severity, but not with physician-assessed global PASI. The data suggest that OCT may be used to measure ET in psoriasis and the measurements correlate with several other parameters of disease severity. This implies that OCT assessment of psoriatic plaques may provide a useful method for non-invasive in vivo method to follow the evolution of psoriasis lesions.