Objectives: Vertebral augmentation (VA) has become routinely used in vertebral compression fractures (VCFs). VCFs are often associated with posterior wall protrusions (PWPs), which theoretically contraindicates vertebroplasty due to a higher risk of neurological complications. The latest generation of VA devices uses intravertebral cranio-caudal expandable implants to improve the correction of structural deformities but could also be used to prevent further PWP during cement injection. The aim of this study was to evaluate the safety of VA with expandable implant for VCFs with PWP. Methods: All consecutive patients treated with expandable implants were considered eligible for inclusion if they met the following criteria: (1) non-neurological VCF, (2) considered unstable (A3-A4 in AOSpine classification), (3) significant PWP (> 2 mm), (4) back pain with a visual analogue scale (VAS) ≥ 4. PWPs were independently measured by two investigators; Pearson's statistics were used for interobserver reproducibility. Results: Fifty-one consecutive patients, with a mean age of 75 ± 8.3 years (range, 50-92), were included. There was a slight decrease between mean preoperative (6.7 mm ± 2.2 mm) and postoperative (6.5 mm ± 2.2 mm) PWP (p = 0.02), with an excellent interobserver reproducibility (Pearson correlation coefficient = 0.92). A mean kyphosis reduction of 34.9% (± 28.4) was observed (p < 0.001). Forty-two patients (82.4%) had significant pain improvements (mean preoperative VAS = 6.9 [± 1.7] versus 3.1 [± 2.0] postoperatively [p < 0.001]). Secondary adjacent level fractures were noted in 16 patients (31.4%), with a reduction of that risk down to 18.8% if a preventive adjacent vertebroplasty was performed, without reaching the significance threshold (p = 0.14). Conclusions: VA with expandable implants appeared safe for non-neurological VCFs with PWP, while allowing satisfactory pain relief.