Performance validity tests (PVTs) are widely used in attempts to quantify effort and/or detect negative response bias during neuropsychological testing. However, it can be challenging to interpret the meaning of poor PVT performance in a clinical context. Compensation-seeking populations predominate in the PVT literature. We aimed to establish base rates of PVT failure in clinical populations without known external motivation to underperform. We searched MEDLINE, EMBASE and PsycINFO for studies reporting PVT failure rates in adults with defined clinical diagnoses, excluding studies of active or veteran military personnel, forensic populations or studies of participants known to be litigating or seeking disability benefits. Results were summarised by diagnostic group and implications discussed. Our review identified 69 studies, and 45 different PVTs or indices, in clinical populations with intellectual disability, degenerative brain disease, brain injury, psychiatric disorders, functional disorders and epilepsy. Various pass/fail cut-off scores were described. PVT failure was common in all clinical groups described, with failure rates for some groups and tests exceeding 25%. PVT failure is common across a range of clinical conditions, even in the absence of obvious incentive to underperform. Failure rates are no higher in functional disorders than in other clinical conditions. As PVT failure indicates invalidity of other attempted neuropsychological tests, the finding of frequent and unexpected failure in a range of clinical conditions raises important questions about the degree of objectivity afforded to neuropsychological tests in clinical practice and research.