Introduction An accurate hemostasis in surgical practice is as important as reduced the dimensions of the operating field are. The need of an optimal, atraumatic hemostasis has become impelling in neurosurgery. Gelified hemostatic matrix has been employed very often because of their simple and safe use. This prospective study is aimed to comparatively evaluate two different hemostatics, Floseal and Surgiflo, in the bleeding control during spine surgery, considering their efficacy, security, and ease of use. Material and Methods From January 2012 to December 2013, 149 patients were recruited for this study. Inclusion criteria were: age between 25 and 80 years, diagnosis of arthrosic or traumatic pathology of lumbar or thoracolumbar spine, persistent bleeding not responding to standard hemostatic techniques. All patients required laminectomy or laminoartrectomy, with exposure of the perivertebral venous plexus. Aim of our study was to reach a complete stop of the bleeding in the operatory field after the application of hemostatic gel. All patients have been evaluated during the follow-up period with clinical and neurological examination after the intervention. All patients underwent a CT scan 3 months after the intervention. Results We included 149 patients in our study: 98 men and 51 women. A total of 92 patients were affected by a degenerative condition, 57 by traumatic pathology. A total of 42 patients assumed anticoagulant and/or antiaggregant therapy preoperatively. In all cases, a massive bleeding originated from the epidural venous plexus. Floseal was used in 86 cases, Surgiflo in 63. A complete hemostasis was achieved in all patients in a time included between 3 minute 30 second and 7 minute (Floseal 5 minute 35 second ± 52 second, Surgiflo 5 minute 32 second ± 54 second). Statistical analysis did not show any association between coagulation time and hemostatic, age, sex, pathology treated. A previous therapy with antiaggregants and/or anticoagulants determined a slight increase in time of hemostasis without any statistical difference. The clinical and radiological follow-up showed no evidence of postsurgical hematomas. Conclusion Comparative analysis of the two products did not show any relevant difference in terms of efficacy and ease of use, showing their effectiveness in the bleeding control. Their use has been valid even in patients who made use of antiaggregant/anticoagulant drugs preoperatively. Both Floseal and Surgiflo can be considered a valid instrument in controlling bleedings in thoracic and lumbar spine surgery.