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Substantial sums of money are being invested worldwide in health information technology. Realising benefits and mitigating safety risks is however highly dependent on effective integration of information within systems and/or interfacing to allow information exchange across systems. As part of an English programme of research, we explored the social and technical challenges relating to integration and interfacing experienced by early adopter hospitals of standalone and hospital-wide multimodular integrated electronic prescribing (ePrescribing) systems.We collected longitudinal qualitative data from six hospitals, which we conceptualised as case studies. We conducted 173 interviews with users, implementers and software suppliers (at up to three different times), 24 observations of system use and strategic meetings, 17 documents relating to implementation plans, and 2 whole-day expert round-table discussions. Data were thematically analysed initially within and then across cases, drawing on perspectives surrounding information infrastructures.We observed that integration and interfacing problems obstructed effective information transfer in both standalone and multimodular systems, resulting in threats to patient safety emerging from the lack of availability of timely information and duplicate data entry. Interfacing problems were immediately evident in some standalone systems where users had to cope with multiple log-ins, and this did not attenuate over time. Multimodular systems appeared at first sight to obviate such problems. However, with these systems, there was a perceived lack of data coherence across modules resulting in challenges in presenting a comprehensive overview of the patient record, this possibly resulting from the piecemeal implementation of modules with different functionalities. Although it was possible to access data from some primary care systems, we found poor two-way transfer of data between hospitals and primary care necessitating workarounds, which in turn led to the opportunity for new errors associated with duplicate and manual information transfer. Extending ePrescribing to include modules with other clinically important information needed to support care was still an aspiration in most sites, although some advanced multimodular systems had begun implementing this functionality. Multimodular systems were, however, seen as being difficult to interface with external systems.The decision to pursue a strategy of purchasing standalone systems and then interfacing these, or one of buying hospital-wide multimodular systems, is a pivotal one for hospitals in realising the vision of achieving a fully integrated digital record, and this should be predicated on a clear appreciation of the relative trade-offs between these choices. While multimodular systems offered somewhat better usability, standalone systems provided greater flexibility and opportunity for innovation, particularly in relation to interoperability with external systems and in relation to customisability to the needs of different user groups.