Introduction. Mental illness and aggression are often seen as inextricably linked. There is a growing body of evidence on aggressive behavior towards others by people with schizophrenia. Even though there is no study conducted in this study area, this study will help to identify the factors associated with aggressive behavior to be dealt early and as a base line for further study. Therefore, this study was designed to determine the prevalence of aggressive behavior and associated factors among people with schizophrenia. Method. An institutional-based cross-sectional study was conducted at Ayder Comprehensive Specialized Hospital from May 6 to 31, 2019, among 403 participants who were selected by a systematic random sampling technique. Data was collected by an interview technique by using the Modified Overt Aggression Scale, entered and analyzed by using EPI-INFO version 3.5.3 and Statistical Package for Social Science version 20, respectively. The association between variables was analyzed using bivariate and multivariate logistic regression analyses, and the level of significance of association was determined at a P value < 0.05. Results. A total of 403 schizophrenia patients were included making the response rate 95.4%. The prevalence of aggressive behavior was 26.6%. Significant associated factors for aggressive behavior were being male (AOR=2.61, 95% CI (1.21, 5.61)), unemployment (AOR=8.03, 95% CI (3.08, 25.95)), previous history of aggression (AOR=6.22, 95% CI (2.75, 14.10)), psychotic symptoms (AOR=8.12, 95% CI (3.11, 21.14)), drug nonadherence (AOR=6.41, 95% CI (3.02, 13.63)), poor social support (AOR=3.11, 95% CI (1.35, 7.17)), and alcohol use (AOR=2.40, 95% CI (1.02, 5.66)). Conclusion. Prevalence of aggressive behavior is high among schizophrenia patients. Professionals have to identify clearly predictors of aggressive behavior giving special emphasis when treating male schizophrenia patients, who are unemployed, lack social support, with previous history of aggression, and alcohol users.