Injuries resulting from manual handling tasks represent an on-going problem for the transport and storage industry. This article describes an application of a systems theory-based approach, Rasmussen’s (1997) risk management framework, to the analysis of the factors influencing safety during manual handling activities in a freight handling organisation. Observations of manual handling activities, cognitive decision method interviews with workers (n = 27) and interviews with managers (n = 35) were used to gather information about three manual handling activities. Hierarchical task analysis and thematic analysis were used to identify potential risk factors and performance shaping factors across the levels of Rasmussen’s framework. These different data sources were then integrated using Rasmussen’s Accimap technique to provide an overall analysis of the factors influencing safety during manual handling activities in this context. The findings demonstrate how a systems theory-based approach can be applied to this domain, and suggest that policy-orientated, rather than worker-orientated, changes are required to prevent future manual handling injuries.