Considerable effort and resources have been dedicated to improving the quality and safety of patient care through health information systems, but there is still significant scope for improvement. One contributing factor to the lack of progress in patient safety improvement especially where technology has been deployed relates to an over-reliance on purely objective, quantitative, positivist research paradigms as the basis for generating and validating evidence of improvement. This paper argues the need for greater recognition and accommodation of evidence of improvement generated through more subjective, qualitative and pragmatic research paradigms to aid patient safety especially where technology is deployed. This paper discusses how acknowledging the role and value of more subjective ontologies and pragmatist epistemologies can support improvement science research. This paper illustrates some challenges and benefits from adopting qualitative research methods in patient safety improvement projects, particularly focusing challenges in the technological era. While adopting methods that can more readily capture, analyse and interpret direct user experiences, attitudes, insights and behaviours in their contextual settings, patient safety can be enhanced ‘on the ground’ and errors reduced and/or mitigated, challenges of using these methods with the younger “technologically-centred” healthcare professionals and patients needs to recognised.