OBJECTIVES: The Quality of Life (QoL) impact of chronic hand eczema (CHE) is expected to be significant because of the high functional, social and psychological impact of this disease but has rarely been assessed with validated tools. This study determined the effect of CHE severity on patient QoL by the Dermatology Life Quality Index (DLQI). METHODS: Data from a Phase II study of oral alitretinoin for the treatment of moderate to severe CHE unresponsive to potent topical corticosteroids was used to measure changes in QoL according to Physician’s Global Assessment (PGA) of disease severity. 162 matched DLQI and PGA observations were analysed using mixed models. The PGA is a global 5-point rating of CHE severity based on multiple signs and symptoms. The DLQI is a simple questionnaire validated in several skin diseases and different languages. Ten questions scored 0–3 are summed, with a total score of  0 (best QoL) to 30 (worst QoL). DLQI > 5 is considered clinically significant and DLQI 11-20 is considered to indicate a very large impact of skin disease on QoL. RESULTS: Increasing severity of CHE was associated with a conditional mean DLQI score as follows: ‘clear/almost clear’ 1.74, ‘mild’ 5.93, ‘moderate’ 9.78, and ‘severe’ 15.08.  Changes in DLQI score from PGA ‘severe’ to milder states during the 12 week study were as follows: ‘moderate’ (-5.30), ‘mild’ (-9.15), ‘almost clear’ (-12.03), and ‘clear’ (-14.56). All changes were statistically significant (p<0.0001) and exceeded the Minimal Important Difference (MID) for CHE estimated to be 2.53 in a recent German observational study. CONCLUSIONS: The QoL of patients with CHE is significantly influenced by clinical disease severity as measured by the PGA instrument.  Treatment which reduces clinical severity of CHE is likely to be worthwhile from the patient perspective in view of the significant improvement in QoL that may result.