Introduction: Learning health systems (LHS) are one of the major computing advances in health care. However, no prior research has systematically analysed barriers and facilitators for LHS. This paper presents an investigation into the barriers, benefits, and facilitating factors for LHS in order to create a basis for their successful implementation and adoption. Methods: First, the ITPOSMO-BBF framework was developed based on the established ITPOSMO (information, technology, processes, objectives, staffing, management, and other factors) framework, extending it for analysing barriers, benefits, and facilitators. Second, the new framework was applied to LHS. Results: We found that LHS shares similar barriers and facilitators with electronic health records (EHR); in particular, most facilitator effort in implementing EHR and LHS goes towards barriers categorised as human factors, even though they were seen to carry fewer benefits. Barriers whose resolution would bring significant benefits in safety, quality, and health outcomes remain.LHS envisage constant generation of new clinical knowledge and practice based on the central role of collections of EHR. Once LHS are constructed and operational, they trigger new data streams into the EHR. So LHS and EHR have a symbiotic relationship. The implementation and adoption of EHRs have proved and continues to prove challenging, and there are many lessons for LHS arising from these challenges. Conclusions: Successful adoption of LHS should take account of the framework proposed in this paper, especially with respect to its focus on removing barriers that have the most impact.