BackgroundHospital pharmacists play a central role in medication safety activities. However, in Ethiopia, this role has been launched recently and little is known regarding the current status of this extended service. Using the Theoretical Domains Framework (TDF), we aimed to identify the barriers and facilitators to hospital pharmacists’ engagement in medication safety activities across various public hospitals in the Amhara region of Ethiopia.MethodsEight focus group discussions, using an interview guide that was drawn upon the TDF, were conducted with 44 hospital pharmacists to explore their beliefs regarding their involvement in clinical services. Group discussions were audio-recorded, transcribed verbatim, and analysed using directed content analysis based on the TDF. Relevant domains were identified by applying relevance criteria to each of the domains in the TDF.ResultsContent analysis revealed six domains that influence hospital pharmacists’ engagement in medication safety activities. These domains included ‘Knowledge’, ‘Skills’, ‘Environmental context and resources’, ‘Motivations and goals’, ‘Social influences’ and ‘Social/professional role’. Most hospital pharmacists believed knowledge gap was an issue, as was the lack of training and supportive skills although some expressed as they were competent enough for their skills in identifying medication related problems. Most participants were very much enthusiastic for their extended roles and were positive towards the future of the profession; however, competing priorities along with the lack of remuneration and awareness (of other health care professionals) regarding the profession’s role were barriers to service delivery. There were also a number of resource constraints, such as staffing, infrastructure and government funding, and acceptance rate of pharmacist’s recommendation that were likely to influence the clinical practice of pharmacists.ConclusionUsing the TDF, this study identified a wide range of barriers and facilitators to hospital pharmacists’ engagement in medication safety activities in resource-limited settings. There existed considerable interrelationships between domains that were perceived to influence hospital pharmacists’ behaviours, and this may assist in designing behaviour change interventions that target common behavioural domains.Electronic supplementary materialThe online version of this article (10.1186/s40545-018-0129-y) contains supplementary material, which is available to authorized users.