Purpose <p>To derive common patterns (trajectories) of work absence over time due to a musculoskeletal (MSK) or mental health (MH) condition in an English population and determine associations of these absence trajectories with health and sociodemographic characteristics.</p> Methods <p>This retrospective cohort study used primary care data for 43,130 and 62,355 economically active individuals with an incident work absence (as measured by receipt of fit notes) due to a MSK or MH condition, respectively, between 2016 and 2018. Latent class growth analysis was used to define trajectories (through issuance of fit notes), and trajectory-covariate association analysis was performed through multivariable multinomial logistic regression.</p> Results <p>Five common trajectories of work absence associated with MSK and MH conditions were determined over a one-year follow-up. The two most common trajectories consisted of low absence (a ‘Single’ fit note and ‘Short Term’ absence), while the two least common trajectories were characterized by longer-term absence of six months or more (‘Chronic Sustained’ and ‘Chronic Fast Decreasing’), and the fifth by intermittent absence. Individuals associated with the two longer-term absence trajectories were older, living in the North or Midlands or most deprived areas of England, prescribed opioids, and current smokers.</p> Conclusions <p>This study has highlighted different patterns of sickness absence due to a MSK or MH condition and profiles of individuals associated with longer-term absence. Earlier and more targeted health and work intervention toward these high-risk subgroups, alongside policy interventions to reduce health inequalities, could help alleviate the rising rate of long-term sickness absence and economic inactivity.</p>