Appropriate scale validity and internal consistency reliability have recently been documented for the new thyroid-specific quality of life (QoL) patient-reported outcome (PRO) measure for benign thyroid disorders, the ThyPRO. However, before clinical use, clinical validity and test-retest reliability should be evaluated. To investigate clinical ('known-groups') validity and test-retest reliability of the Danish version of the ThyPRO. For each of the 13 ThyPRO scales, we defined groups expected to have high versus low scores ('known-groups'). The clinical validity (known-groups validity) was evaluated by whether the ThyPRO scales could detect expected differences in a cross-sectional study of 907 thyroid patients. Test-retest reliability was evaluated by intra-class correlations of two responses to the ThyPRO 2 weeks apart in a subsample of 87 stable patients. On all 13 ThyPRO scales, we found substantial and significant differences between the groups expected to have high versus low scores. Test-retest reliability was above 0.70 (range 0.77-0.89) for all scales, which is usually considered necessary for comparisons among patient groups, but below 0.90, which is the usual threshold for use in individual patients. We found support for the clinical validity of the new thyroid-specific QoL questionnaire, ThyPRO, and evidence of good test-retest reliability. The questionnaire is now ready for use in clinical studies of patients with thyroid diseases.