Objective We performed this study to investigate whether the use of closed-suction drainage following microvascular decompression (MVD) causes cerebrospinal fluid (CSF) leakage. Methods Between 2004 and 2011, a total of 157 patients with neurovascular compression were treated with MVD. MVD was performed for hemifacial spasm in 150 (95.5%) cases and for trigeminal neuralgia in 7 (4.5%) cases. The mean age of the patients was 49.8±9.6 years (range, 20-69). Dural substitutes were used in 44 (28.0%) patients. Ninety-two patients (58.6%) were underwent a 4-5 cm craniotomy using drainage (drainage group), and 65 (41.4%) did a small 2-2.5 cm retromastoid craniectomy without closed-suction drainage (no-drainage group). Results Eleven (7.0%) patients experienced CSF leakage following MVD based on the criteria of this study; all of these patients were in the drainage group. In the unadjusted analyses, the incidence of CSF leakage was significantly related with the use of closed-suction drainage following MVD (12.0% in the drainage group vs. 0% in the no-drainage group, respectively; p=0.003; Fisher's exact test). Those who received dural substitutes and the elderly (cut-off value=60 years) exhibited a tendency to develop CSF leakage (p=0.075 and p=0.090, respectively; Fisher's exact test). In the multivariate analysis, only the use of closed-suction drainage was significantly and independently associated with the development of CSF leakage following MVD (odds ratio=9.900; 95% confidence interval, 1.418 to infinity; p=0.017). Conclusion The use of closed-suction drainage following MVD appears to be related to the development of CSF leakage.