Depression is a mental illness affecting more than 260 million people worldwide. In Greenland, the prevalence of patients treated with antidepressant medicine (antidepressants) has not previously been investigated. The aim of this study was to estimate and compare the age-and gender-specific prevalence of patients treated with antidepressants in Greenland and Denmark. The study was a cross-sectional register study using data from population and medical registers in Greenland and Denmark. Included was 1,573 Greenlandic patients and 419,151 Danish patients treated with antidepressants, respectively. The overall prevalence of patients aged 10-89 years treated with antidepressants was 3.5% in Greenland, and 8.1% in Denmark, being significantly lower in Greenland compared to Denmark (p < 0.001). The age-and gender-specific prevalence was significantly lower for patients from Greenland compared to from Denmark. In both Greenland and Denmark, the prevalence of women receiving antidepressants was significantly higher than for men. Finally, there was regional differences in the prevalence of usage of antidepressants in Greenland. Undiagnosed depression might contribute to the lower prevalence in Greenland as well as limited access to primary healthcare.