Polypharmacy is the use of multiple drugs by a patient at the same time and is common in the elderly. To our knowledge, drug use patterns in Somaliland are rarely studied. The purpose of this study was to evaluate polypharmacy, drug use patterns, and their predictors at the Edna Adan University Hospital in Hargeisa, Somaliland. A retrospective cohort analysis of 1140 medical records and prescriptions over a year from August 28, 2019, to August 27, 2020, was reviewed. The data completeness and consistency were checked and entered with the SPSS version 25.0. The association between total polypharmacy and different variables was analyzed using multivariable binary logistic regression and expressed as an odds ratio (OR) and 95% confidence interval (CI). In addition, the World Health Organization’s core drug use and facility indicators were used to assess the drug use patterns. The overall polypharmacy in this study was 71%. Statistically significant association was observed between the polypharmacy and variables such as age ( P = 0.01 ; OR = 3.4, 95% CI = 1.9–6.1), chronic illness ( P = 0.01 , OR = 8.6, 95% CI = 5.1–14.7), and comorbidity ( P = 0.01 , OR = 5.2, 95% CI = 2.1–12.9). However, the ward admitted/visited and gender did not have a statistically significant association with polypharmacy. There was overuse of brand drugs (63.9%) and antibiotics (55.2%), while the use of injectables (19.9%) was within the acceptable range. Polypharmacy and overuse of brand drugs and antibiotics were prevalent in the study setting. Essential drugs list, formularies, and treatment and regulatory guidelines are needed in place to ensure appropriate drug use.