Background: Hand eczema is a disease with large variation in clinical presentation and severity. Scoring systems for quantitative severity assessment exist. However, they are observer-dependent. An objective quantitative tool for scoring of hand eczema would improve categorization of hand eczema. Objective: To investigate the usefulness of multispectral imaging in assessing severity of hand eczema with respect to extent and the different morphological features. Methods: Patients with hand eczema (n = 60) and healthy controls (n = 28) were included. The severity of hand eczema was assessed by a dermatologist using the Hand Eczema Severity Index (HECSI) and a global assessment (Physician Global Assessment [PGA]). Multispectral imaging of the hand was performed on all patients and controls using the VideometerLab Instrument. Results: Areas of the morphological elements identified by multispectral imaging were statistically significantly correlated with the PGA scores. Analyzed by Cohen's kappa, a moderate agreement between imaging-based severity assessment and PGA was found. The imaging-based severity assessment was also correlated with HECSI (Spearman rho 0.683, P <.001). Still, the imaging-based algorithm was not capable of differentiating hand eczema patients from controls. Conclusions: Multispectral imaging allows quantitative measurements of different skin parameters to be performed. In its present form, multispectral imaging cannot replace the clinical assessment of a dermatologist. However, after refinement, this or similar technologies could prove useful.