Neurosurgical hemostasis can be performed with bipolar coagulation and with the support of several dedicated biomaterials including oxidized regenerated cellulose (ORC; e.g., Surgicel®, Johnson & Johnson, New Brunswick, NJ, USA). Oxidized regenerated cellulose is a sterile absorbable fibrous biomaterial that has become a major local hemostatic agent thanks to its ease of use, favorable biocompatibility and bioabsorption characteristics. However, some postoperative issues associated with its use, such as allergic reaction, seroma, foreign-body reaction with compressive neuropathies and misdiagnosis during follow-up, have been reported. These complications could compromise clinical outcomes with a negative impact on patient quality of life and sometimes require risky major surgical procedures. An understanding of the specific properties of ORC combined with adequate surgical expertise and compliance with some basic rules are needed to optimize clinical outcomes and minimize postoperative issues.