Eighteen randomized controlled trials including 1,752 patients with osteoporotic vertebral compression fractures were included in this systematic review and meta-analysis comparing unilateral percutaneous kyphoplasty (PKP) vs. bilateral PKP. Pooled outcomes of interest included operative time, volume of bone cement injected, cement leakage, radiation exposure, visual analog scale (VAS) scores for pain, Oswestry Disability Index (ODI), and kyphotic angle improvement. The meta-analysis found that unilateral PKP had a shorter operative time, lower bone cement volume, and lower radiation exposure compared to bilateral PKP, while maintaining comparable results in pain relief, disability index, and kyphotic angle improvement. These findings suggest that unilateral PKP is a better clinical option for OVCFs due to its reduced procedural complexity and similar clinical efficacy.