Sedentary office work has been shown to cause low back discomfort and potentially cause injury. Prolonged standing work has been shown to cause discomfort. The implementation of a sit-stand paradigm is hypothesised to mitigate discomfort and prevent injury induced by prolonged exposure to each posture in isolation. This study explored the potential of sit-stand to reduce discomfort and prevent injury, without adversely affecting productivity. Twenty-four participants performed simulated office work in three different conditions: sitting, standing and sit-stand. Variables measured included: perceived discomfort, L4-L5 joint loading and typing/mousing productivity. Working in a sit-stand paradigm was found to have the potential to reduce discomfort when compared to working in a sitting or standing only configuration. Sit-stand was found to be associated with reduced lumbar flexion during sitting compared to sitting only. Increasing lumbar flexion during prolonged sitting is a known injury mechanism. Therefore, sit-stand exhibited a potentially beneficial response of reduced lumbar flexion that could have the potential to prevent injury. Sit-stand had no significant effect on productivity. Practitioner Summary: This study has contributed foundational elements to guide usage recommendations for sit-stand workstations. The sit-stand paradigm can reduce discomfort; however, working in a sit-stand ratio of 15:5 min may not be the most effective ratio. More frequent posture switches may be necessary to realise the full benefit of sit-stand.