Background. An adverse drug reaction (ADR) is harm that arises from the use of a drug. Adverse drug reactions have a huge impact on the health system since they result in drug-related morbidity and mortality as well as indirect costs such as loss of productivity at work. Reporting of adverse drug reactions to a relevant authority is one of the methods of enhancing medication safety; however, underreporting of adverse drug reactions by health workers is a major challenge in enhancing medicines safety. The aim of this study was to assess the willingness, attitude, and associated factors of healthcare providers towards ADRs reporting at Mizan Tepi University Teaching Hospital (MTUTH). Methods. A cross-sectional mixed method was conducted among healthcare providers working in Mizan Tepi University Teaching Hospital from August to September 2021. A total of 190 healthcare providers and five key informants were participated in the study. The quantitative data were collected using self-administered structured questionnaires, and for the qualitative study, data from the key informant interviews were collected using a semistructured questionnaire containing open-ended questions. The collected data were coded, entered, and analyzed using a Statistical Package for Social Sciences (SPSS, version 21). Furthermore, the logistic regression model was fitted to see the association between attitude items and demographic characteristics. Variables with
P
value <0.05 were considered as statistically significant. Analysis of the qualitative data was done by sorting the data into categories and examining the emerging themes. Results. The majority of individuals in the study (81.6%) were willing to report adverse drug reactions. High percent (57.9%) of the study participants knew how to report ADR to responsible body and 66 (34.7%) of the study participants believe that ADR reporting is the responsibility of all healthcare professionals. 86 (45.3%) of respondents encountered ADR cases during their professional career. It was found that the majority of participants (53.7%) had a positive attitude toward ADR reporting. The professional distribution and work experiences of healthcare professionals had a significant impact on their attitude toward ADR reporting (
P
<
0.05
). Conclusion. A large percentage of study subjects were willing to report adverse drug reactions to the appropriate authorities. The majority of healthcare providers were found to have a good attitude towards ADR reporting. Professional distribution and work experiences were significantly associated with attitude of healthcare providers towards ADR reporting. In order to improve the ADR reporting practices of the healthcare professionals and increase the ADR reporting load at the national level, the national regulatory body should collaborate with health facilities.