Despite the high prevalence of withdrawal from employment gained post-traumatic spinal cord injury (tSCI), relatively few studies have examined the factors that precipitate job withdrawal. Within the context of general systems theory, the aim of the present study was to identify and classify the factors that led to job withdrawal post-tSCI. Using purposive sampling and a structured proforma, 30 participants completed an in-depth telephone interview. Job withdrawal was precipitated more frequently by micro-system (person-centred) factors or meso-system (job-related) factors than macro-system (socio-economic) factors. Micro-system factors fell into five groups (SCI-related, psychological/psychosocial, mobility, general health and knowledge/skills/abilities) as did meso-system factors (job design, psychosocial climate, ergonomics, human resources and work cycles). Two groups of macro-system factors were identified (proximal and distal). Classifying job withdrawal factors within the context of general systems theory provides an integrated framework for intervention development and furnishes decision-makers with guidance as to whether a top-down or bottom-up approach would be more feasible/beneficial to address preventable job withdrawal post-tSCI.