Background: How changes in hand eczema (HE) severity correlate with the single scores on the Hand Eczema Severity Index (HECSI) is sparsely investigated and particularly needed in clinical trials. Objectives: To find the minimal important change (MIC) for HECSI based on patient's and physician's assessments using different methods. Methods: In this prospective follow-up study, three different anchors were used: two anchor questions for patients and physician, respectively, and the Physician Global Assessment (PGA) with a photographic guide. MIC was estimated by mean change in patients with a one-step increase to anchor-questions, receiver-operating characteristic (ROC) plot, and smallest detectable change (SDC). Results: One hundred fifty-two patients with HE (63.8% female) were included at baseline (89% completed follow-up). The mean change, ROC cutoff, and SDC values were 7.1, 4.5, 21.4 (patient-rating), 8.2, 4.5, 8.3 (physician-rating), and 16.6, 6.5, 27.1 points (PGA), respectively. SDC stratified by baseline severity was 2.9 and 11 points for mild and moderate-severe HE (physician-rating), respectively. Conclusion: Identification of the MIC for the HECSI is important in relation to evaluation of treatment, intervention, and sample-size calculations. An improvement of 8.3 points on the HECSI is recommended as the MIC. MIC values may differ according to baseline severity, and this variation should be clarified in future studies.