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Determining factors predictive of ventriculoperitoneal shunt failure in a cohort of adults. OBJECTIVE: Despite being one of the most frequently performed neurosurgical procedures, there is lack of consensus on the factors that predict failure after ventriculoperitoneal (VP) shunt placement. The aim of this study was to contribute data from a large single-center cohort and discuss measures to address the variables identified, adding to the literature on this subject. METHODS: All patients ≥ 18 years of age who underwent initial VP shunt placement from January 2015 to April 2021 at our center were included. Demographic and preoperative data, as well as details of the surgery, were collected. The occurrence of failure, including the time to failure and the causes and sites of failure, were assessed. RESULTS: This study included 1425 patients (mean age 41.8 ± 15.1 years; 793 male, 632 female). Over a mean follow-up of 42 months, failure occurred in 120 patients (8.4%) at a mean time to revision of 2.9 months. Multivariate analysis identified a left-sided location (HR 4.602, 95% CI 2.893-7.320, p < 0.001), a single operating surgeon (HR 2.793, 95% CI 1.904-3.984, p < 0.001), placement at night (HR 2.994, 95% CI 2.136-4.184, p < 0.001), and entry at Kocher's point (HR 1.949, 95% CI 1.068-3.558, p = 0.029) as predictive of shunt failure, while posthemorrhagic and postmeningitic hydrocephalus remained significantly associated with early shunt failure (HR 3.058, 95% CI 1.308-7.142, p = 0.010), as did CSF protein levels > 100 mg/dL (HR 2.849, 95% CI 1.103-7.352, p = 0.03). CONCLUSIONS: Failure of VP shunts occured in 8.4% of adult patients. A left-sided shunt, a single operating surgeon, shunts placed at night, and entry at Kocher's point were significantly associated with shunt failure. Although not associated with overall shunt failure, posthemorrhagic and postmeningitic hydrocephalus and CSF protein levels > 100 mg/dL were significantly associated with early shunt failure.