Abstract Background Studies have documented loss of work capacity and work productivity loss in multiple sclerosis (MS). Little is known about the longitudinal trajectories of work productivity in MS. Objectives To explore trajectories of work productivity in people living with multiple sclerosis (PwMS) and examine the baseline factors linked with assignment to the trajectories group. Methods Study participants were from the Australian MS Longitudinal Study (AMSLS) from 2015 to 2018 who were employed with ≥2 datapoints (n = 1205). We used group-based trajectory modelling to identify unique work productivity trajectories in PwMS. Multinomial logistic regression was used to assess associations with the work productivity trajectories. Results We identified three distinct trajectories of work productivity: ‘moderately worsened’ (16.7%) with a mean work productivity of 47.6% in 2015, ‘mildly worsened’ (50.1%) with a mean work productivity of 86.3% in 2015 and ‘normal’ (33.2%) with a mean work productivity of 99.7% in 2015. On multivariable analysis, the relative probability of being in moderately or mildly worsened work productivity trajectory were higher for baseline factors such as higher education level, longer disease duration, higher disability score, and high MS symptom severity. For example, the relative probability of being in ‘moderately worsened’ rather than ‘normal’ work productivity trajectory increased by 94% (RRR:1.94 ; 95% confidence interval:1.68 - 2.25) for each unit increase in ‘fatigue and cognitive symptoms’ cluster. Conclusion Education level, disability and MS symptom severity increased the probability of following low work productivity trajectory. Key messages Work productivity interventions should target MS symptom severity and disability reduction.