Background: As lifetime expectancy in Greenland is steadily increasing, so is the proportion of elderly Greenlanders. Old age is associated with polypharmacy, and in this study, we aim to describe the prevalence and characteristics of polypharmacy among the care home residents in Greenland. Methods: Eight care homes in Greenland were visited between 2010 and 2016. Questionnaires including information on prescribed medication and comorbidities were collected and analyzed. Drugs were categorized according to Anatomical Therapeutic Chemical (ATC) category, and potential drug–drug interactions (pDDIs) were assessed using the Danish Interaction Database. Polypharmacy was defined as five or more prescribed drugs. Results: All 244 eligible residents were included in the study. The median number of prescribed drugs per resident was six, and women were prescribed more drugs than men (median six versus five). More than 60% of all residents fulfilled the criteria for polypharmacy. The residents in the polypharmacy group had a higher body mass index (26.9 versus 24.3) and more chronic diseases (median two versus one), and more often pulmonary (14% versus 1%) or endocrine disease (22% versus 2%) than in the non-polypharmacy group. The most prescribed drugs belonged to ATC category N (nervous system, 78% of the residents). Finally, pDDIs were found among 61% of the residents and were more common in the capital (77%), which also had the highest proportion of residents with polypharmacy (77%). Conclusion: This is the first study to describe the patterns of polypharmacy and pDDIs among the elderly in care homes in Greenland. Our findings indicate that polypharmacy is as common in Greenland as elsewhere in the Western world, but there are local differences in the prevalence. Plain Language Summary Polypharmacy among the elderly in care homes in Greenland The lifetime expectancy of the Greenlandic population is increasing, and so is the number of elderly Greenlanders. Previous studies have shown that the elderly have a higher risk of being treated with five drugs or more which is called polypharmacy. Polypharmacy can cause unwanted interactions and side effects. In this study, we examine the characteristics of the residents in Greenlandic care homes belonging to this group. Using questionnaires, we gathered information from 244 residents from care homes in eight different towns and settlements in Greenland. Data included types of medication prescribed to the resident, age, gender, cause of stay, and medical history, which allowed us to compare the results between genders and towns. We found that among 244 residents, more than half of all residents were prescribed five or more different drugs, and women were generally prescribed more drugs than men. Those prescribed five or more drugs had a higher body mass index and more diseases than those prescribed fewer drugs. We also found that certain types of medication, mainly painkillers, were the most prescribed. Finally, residents in the care home in Greenland’s capital Nuuk were more often prescribed five or more drugs than elsewhere in Greenland, indicating local differences in Greenland. Our results give an essential insight into the health and medication of the most fragile elderly in Greenland. Polypharmacy seems to be as common here as elsewhere in the Western world and is a point of focus.