This study evaluates whether the fracture level alters the outcomes of minimally invasive hybrid stabilization (MIHS) with double-threaded, uncemented polyaxial screws for unstable osteoporotic vertebral fractures. This prospective cohort study included 73 patients (71.23% females, mean age: 79.9 ± 8.8 years) with unstable OF 3-4 fractures treated by MIHS between Nov 2015-Jan 2018. Patient characteristics, operative data, clinical outcomes, complications, radiological outcomes, and midterm (24-month) follow-up regarding functionality, pain, and quality of life were analyzed. Patients had thoracolumbar (71.23%), thoracic (10.97%), and lumbar (17.8%) fractures. Operative time was < 120min in 73.97% of patients, with blood loss < 500ml in 97.25% of cases. No in-hospital mortality was recorded. Spine-associated complications occurred in 15.07% of patients, while 36.98% of patients had urinary tract infections (n = 12), pneumonia (n = 5), and electrolyte disturbances (n = 9). The mean length of hospital stay was 13.38 ± 7.20 days. Clinically-relevant screw loosening occurred in 1.7% of screws, and secondary adjacent fractures were diagnosed in 5.48% of patients. The alpha-angle improved significantly postoperatively (mean change: 5.4°) and remained stable for 24 months. The beta-angle improved significantly from 16.3° ± 7.5 to 10.8° ± 5.6 postoperatively but increased slightly to 14.1° ± 6.2 at midterm follow-up. Although no differences were seen regarding baseline data, clinical outcomes, and complications, fracture level significantly altered the COMI score at 24 months with no effect on pain score or quality-of-life. MIHS using polyaxial screws is a safe treatment for single-level osteoporotic spinal fractures. Fracture level did not alter radiological reduction loss; however, it significantly altered patients' function at 24 months.