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Background The use of Gamma Knife radiosurgery (GKRS) for recurrent or residual vestibular schwannoma (VS) after microsurgery (MS) has been investigated in several retrospective studies. The purpose of this study was to identify potential risk factors for both neurologic deterioration and tumor progression after GKRS for previously operated VSs in a prospective setting. Methods Patients who underwent GKRS for previously operated and histopathologically confirmed VS between 1998 and 2015 were prospectively followed-up. Risk factors for therapy side effects and predictors for tumor control were investigated in uni- and multivariate analyses. Results A total of 160 individuals with a median age of 55 years were included. Median tumor volume prior to GKRS was 1.40 cm3 (range, 0.06–35.80 cm3). After a median follow-up of 36 months, hearing and facial nerve function were serviceable (modified Gardner-Robertson and House-Brackmann grades I and II) in 7 (5%) and 82 (55%) patients, respectively. Deterioration to a nonserviceable facial nerve function after GKRS was found in 3% (3/89) and tended to increase with rising tumor volume (odds ratio, 1.65 per cm3; 95% confidence interval, 1.00–2.71; P = 0.051). Median tumor volume prior to GKRS was higher in patients with radiologic (P = 0.020) or clinical tumor progression (P < 0.001). Critical tumor volume prior to GKRS to predict clinical and radiologic tumor progression was 1.30 cm3 (P < 0.001) and 3.30 cm3 (P = 0.019), respectively. However, in multivariate analyses, none of the analyzed variables were found to independently predict tumor progression. Conclusions Intended submaximal resection followed by GKRS is a viable treatment for VS. Because tumor remnant size after MS is an important predictor for recurrence after adjuvant GKRS, both brainstem and cerebellar decompression and maximal safely achievable resection should remain major goals of microsurgery. [ABSTRACT FROM AUTHOR]