Background: Surgical intervention is one of the core components of the health care system, yet not free of risks. Once postoperative complications occur, patients are subjected to extra costs for treatment, longer hospital stay, and associated disabilities. The chance of death also increases once patients develop postoperative complications. However, the extent of in-hospital postoperative complications was not well studied in Ethiopia, particularly in the Eastern part of the country. As a result, this study was aimed to determine the magnitude of postoperative complications and to identify associated factors among surgical patients treated at a tertiary hospital, eastern Ethiopia. Methods: A prospective cohort study was conducted from July 1, 2019 to January 30, 2020. Patients from general surgery, neurosurgery, orthopedic, and pediatric surgery were incorporated into the study. The calculated sample size was 384 using single population formulas. Data were analyzed using SPSS version 23. Bivariable and multivariable logistic regression analyses were conducted to identify factors associated with postoperative complications. The significance level of associations was considered with a P-value <0.05 and an adjusted odds ratio (AOR) at a 95% confidence interval(CI). Results: 8The magnitude of postoperative complications was 12.5% (95% CI=9.4-16.2%). From those who had developed postoperative complications, 20.5% were deceased. Factors associated with postoperative complications were cigarette smoking (AOR=4.02, 95% CI=1.86-8.66), patients with a morbidity status according to the American Society of Anesthesiologists (ASA) category 2 (AOR=7.83; 95% CI=2.95-20.75), ASA 3 (AOR=9.62; 95% CI=1.70-54.46), and ASA 4 (AOR=3.25; 95% CI=1.22-8.60), operative hours of 1-2 hours duration (AOR=3.38; 95% CI=1.45-7.94), operative hours of more than 2 hours (AOR=4.36; 95% CI=1.91-9.95), and intraoperative complications (AOR=5.96; 95% CI=1. 707-20.87). Conclusion: This study showed a higher proportion of postoperative complications associated mortality rates compared to similar studies across the world. The majority of patients who developed complications and died were those who were operated on on an emergency basis. This mandates to follow the damage control surgery protocol, though further study might be needed to sort out the likely causes for this increased risk.