As a discipline, design science has traditionally focused on designing products and associated technical processes to improve usability and performance. Although significant progress has been made in these areas, little research has yet examined the role of human behaviour in the design of socio-technical systems (e.g., organizations). Here, we argue that applying organizational psychology as a design science can address this omission and enhance the capability of both disciplines. Specifically, we propose a method to predict malfunctions in socio-technical systems (PreMiSTS), thereby enabling them to be designed out or mitigated. We introduce this method, describe its nine stages, and illustrate its application with reference to two high-profile case studies of such malfunctions: (1) the severe breakdowns in patient care at the UK’s Mid-Staffordshire NHS Foundation Trust hospital in the period 2005–2009, and (2) the fatal Grayrigg rail accident in Cumbria, UK, in 2007. Having first identified the socio-technical and behavioural antecedents of these malfunctions, we then consider how the PreMiSTS method could be used to predict and prevent future malfunctions of this nature. Finally, we evaluate the method, consider its advantages and disadvantages, and suggest where it can be most usefully applied.