Aims: The Dutch Four-Dimensional Symptom Questionnaire (4DSQ) measures distress, depression, anxiety and somatisation, facilitating the distinction between stress-related problems and psychiatric disorder in primary and occupational health care. The aim of the study was to examine the measurement equivalence across the Danish and Dutch 4DSQ. Methods: Danish 4DSQ data were obtained from a cohort of Danish citizens on sick leave for mental-health problems. Dutch 4DSQ data were obtained from a cohort of Dutch employees on sick leave and a cohort of general practice attenders suspected of having mental-health problems. The study samples were matched on age and sex. The 4DSQ scales were assessed for essential unidimensionality using confirmatory factor analysis. Measurement equivalence of the 4DSQ across the groups was assessed using differential item and test functioning (DIF and DTF) analysis. Results: The study groups each consisted of 1363 people (63% female, M age =42 years). The 4DSQ scales proved essentially unidimensional. DIF was detected in 20 items. In terms of Cohen’s effect size, DIF was mostly small or moderate. In terms of effect size, the mean effect on the scale score (DTF) was negligible. Nevertheless, it is recommended to adjust some of the cut-off points for two Danish 4DSQ scales to retain the meaning of these cut-off points in Dutch respondents. Conclusions: The Danish version of the 4DSQ measures the same constructs as the original Dutch questionnaire. Twenty items functioned differently in Danish respondents than in Dutch respondents, but this had only a small impact on the scale scores.