A frequent cause of weaning failure and the resultant long-term artificial ventilation is the generalized weakness syndrome in the sense of critical illness polyneuropathy or polymyopathy. However, hardly any information is presently available regarding the necessary intensity of the diagnostic workup for reaching or excluding a diagnosis with certainty in the neurological examination or regarding the additional diagnostic value of electrophysiological studies in patients receiving long-term acute care suspected of having critical illness polyneuropathy and polymyopathy. Therefore, the goal of this investigation was to address these questions. A total of 280 patients with complicated weaning were included in the study. All patients underwent clinical examination by a specialist in neurology and electrophysiological workup performed by another specialist. Among the patients studied, the greatest possible certainty of the diagnosis (positive predictive value) of the clinical examination was 97.9% [95% confidence interval (CI) 69.4-99.9] and the best certainty of excluding the diagnosis (negative predictive value) was 88.9% (95% CI 82.7-93.0). Thus, in difficult-to-wean patients who were considered to probably have the diagnosis of critical illness polyneuropathy or polymyopathy as assessed by a specialist, little additional information is gained from an electrophysiological study, which is hence dispensable in these cases.