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Introduction: Brucellosis, the most common zoonosis globally, is considered a major public health problem., Objective: A retrospective study was carried out over 21 years (1998-2018) to determine the epidemiological features of human brucellosis in the province of El-Oued (south-eastern Algeria)., Results: 1,832 confirmed cases of human brucellosis were reported during the study period, with an average incidence rate of around 12.26 cases per 100,000 inhabitants. The annual distribution of the incidence was characterized by an increasing trend and a strong fluctuation ; its values ranged between 2.27 and 24.96 per 100,000 inhabitants. The monthly distribution showed that the highest incidence rates were recorded from mid-February to July, with a peak of 2.74 cases per 100,000 inhabitants in April.Human brucellosis has affected all municipalities. The highest incidence rate was observed in border municipalities such as Ben Guecha and Oum Tiour (89.76 and 66.14 per inhabitants, respectively).The incidence in the male population was higher than that of the female at 14.63 versus 9.83 per 100,000 inhabitants, respectively, noting that it increases with age. Individuals over 65 years are the most at risk, with an incidence rate of 22.32 per 100,000 inhabitants., Conclusion: Along with strengthening preventive measures in the population, eliminating brucellosis in animals is the most effective method to protect humans against infection.