BackgroundAdverse drug reactions (ADRs) are a significant public health concern, particularly in limited resource settings where underreporting is prevalent due to various challenges. Mobile health applications (mHealth apps) offer a promising solution to enhance pharmacovigilance by facilitating easier and more efficient ADR reporting. However, despite the increasing availability and use of mHealth apps, there is a lack of evidence on healthcare professionals' willingness to adopt them for ADR reporting in resource-constrained environments. Therefore, this study aimed to assess the willingness of healthcare professionals in Ethiopia to utilize mobile health applications for adverse drug reaction reporting and identify associated factors. MethodsWe carried out a cross-sectional study involving 422 healthcare professionals working in institutional settings. We gathered data through a pretested questionnaire that participants completed themselves. We inputted the data using Epi Data V.4.6 and analyzed it using SPSS V.26. Our analysis involved conducting multivariable logistic regression to identify the factors influencing the likelihood of healthcare professionals using mobile applications to report adverse drug reactions. ResultsThe study involved 389 healthcare professionals. Approximately 301 (77.4 %) of them expressed willingness to utilize mobile applications for reporting adverse drug reactions. The willingness to utilize mobile applications was significantly associated with the type of mobile phone (smart: AOR 3.56; 95 % CI 2.15–5.67), basic computer training (AOR 4.43; 95 % CI 2.27–8.64), mobile health-related training (AOR 1.96; 95 % CI 1.01–3.79), attitude (AOR 4.01; 95 % CI 2.19–7.35), perceived ease of use (AOR 2.91; 95 % CI 1.59–5.23), and perceived usefulness (AOR 2.10; 95 % CI 1.15–3.85). ConclusionsOverall, there was a high proportion of healthcare professionals willing to use mobile devices for reporting drug adverse reactions. Their willingness correlated with factors such as the type of mobile phone, perceived ease of use, attitude, training, and perceived usefulness of mobile applications. With the increasing use of smartphones, motivation among healthcare professionals is rising. Basic computer and mHealth-related training are crucial for enhancing the acceptability of such applications and should be incorporated into future implementations. Taking these factors into account could offer insights into the design and implementation of mobile applications for adverse drug reactions in Ethiopia.