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Background: Persistent critical illness (PerCI) is defined as an intensive care unit (ICU) admission lasting ≥ 10 days. The in-hospital complications associated with its development are poorly understood. Aims: To test whether PerCI is associated with a greater prevalence, rate and specific types of in-hospital complications. Methods: Single-centre, retrospective, observational case-control study. Results: We studied 1200 patients admitted to a tertiary ICU from 2010 to 2015. Median ICU length of stay was 16 days (interquartile range [IQR], 12-23) for PerCI patients v 2.3 days (IQR, 1.1-3.7) for controls, and median hospital length of stay was 41 days (IQR, 22-75) v 8 days (IQR, 4-17) respectively. A greater proportion of PerCI patients received acute renal replacement therapy (37% v 6.8%) or underwent reintubation (17% v 1%) and/or tracheostomy (36% v 0.6%); P < 0.0001. Despite these complications, PerCI patients had similar hospital mortality (29% v 27%; P = 0.53). PerCI patients experienced a greater absolute number of complications (12.1 v 4.0 complications per patient; P < 0.0001) but had fewer exposure-adjusted complications (202 v 272 complications per 1000 hospital bed-days; P < 0.001) and a particularly high overall prevalence of specific complications. Conclusions: PerCI patients experience a higher prevalence, but not a higher rate, of exposure-adjusted complications. Some of these complications appear amenable to prevention, helping to define intervention targets in patients at risk of PerCI. Funding: Austin Hospital Intensive Care Trust Fund., Competing Interests: None declared., (© 2020 College of Intensive Care Medicine of Australia and New Zealand.)