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Objectives Evidence is mounting that poor psychosocial job conditions increase sickness absence, but there is a need for further rigorous prospective research to isolate the influence of psychosocial job quality from other measured and unmeasured confounders. This study used four waves of prospective longitudinal data (spanning 12 years) to investigate the extent to which increases in poor psychosocial job quality are associated with greater relative risk of day of sickness absence.Design Prospective cohort study.Setting Data were from the Australian PATH Through Life cohort study. The analyses adopted hybrid-regression estimations that isolated the effect of within-person change in psychosocial job quality on sickness absence over time.Participants Participants were from a midlife cohort aged 40–44 at baseline (7644 observations from 2221 participants).Primary outcome measure Days sickness absence in the past 4 weeks.Results The results show that after adjusting for a wide range of factors as well as unmeasured between-person differences in job quality, each additional psychosocial job adversity was associated with a 12% increase in the number of days of sickness absence (relative risk ratio: 1.12, 95% CI 1.03 to 1.21). Increases in psychosocial job adversity were also related to greater functional impairment (relative risk ratio: 1.17 (1.05 to 1.30)).Conclusion The results of this study strengthen existing research highlighting the importance of addressing poor psychosocial job quality as a risk factor for sickness absence.