Background: Postoperative sore throat is a common postoperative complication of anesthesia. Complaints range from a minor self- limiting throat irritation to debilitating pain, inability to swallow for several days. Many factors can contribute to postoperative sore throat and the incidence has been found to vary with the method of airway management. Aim: The aim of this study was to determine magnitude and factors associated with post-operative sore throat among adult surgical patients who were operated under general anesthesia in a resource-limited setup at a tertiary care institution, Addis Ababa, Ethiopia. Materials and Methods: Hospital-based, cross-sectional study was conducted from August 1st to September 30th, 2021 in St. Paul's Hospital Millennium Medical Collage among 303 adult patients. Stratified random sampling technique was used to group surgical patients into departments then surgical patients were sampled from each department by using simple random sampling technique. For the study, data was collected using formatted questionnaire. Sore throat and it's severity was assessed and graded once patients were responsive, communicative and cooperative (within 2 hours) then at 6, 12, 24 and 48 hours of post operation. Severity was assessed using Numerical Rating Scale (NRS). Results: Out of 301 patients who had surgery with general anesthesia and completed 48 hours data collection, post-operative sore-throat was found in 48.5% of patients with variable severity. Approximately 71% of them developed post-operative sore-throat with in the first 2 hours of post-surgery. from the multivariate binary logistic regression analysis; Naso-gastric tube insertion , blood-stained tracheal tube on extubation , duration of anesthesia, for two to six hours and for greater than six hours, number of attempts at intubation for two attempts and no laryngoscopy were strongly associated and important predictors of post-operative sore-throat as compared to their counter-parts. Conclusion and Recommendations: Nearly half of surgical patients undergoing general anesthesia had post-operative sore-throat which is considerably high. It is recommended to give attention for patients undergoing long intubation hours (>2 hours), NG tube inserted patients, multiple attempts at intubation and choice of air way equipment during General anesthesia.