Objective: To determine the efficacy and complication of unilateral extrapedicular approach (UEA) and bilateral pedicle approach (BPA) percutaneous kyphoplasty (PKP) in treating thoracolumbar osteoporotic compression fractures. Study Design: A descriptive study. Place and Duration of Study: Department of Orthopaedics, Bazhou district people Hospital, Sichuan, China, from December 2016 to March 2021. Methodology: Patients with single-level thoracolumbar osteoporotic compression fractures, who underwent BPA and UEA PKP, were divided into the UEA (n=47) and BPA group (n=42). Index was recorded including operation duration, bone cement volume, intraoperative X-ray times, complication, visual analogue scale (VAS), Cobb angle, Oswestry dysfunction index (ODI), the recurrence rate of the injured vertebra and adjacent vertebral fractures within 12 months after operation. Results: There were significant differences in operation duration, bone cement volume, and intraoperative X-ray time between the two groups (p<0.05). VAS, Cobb angle, and ODI significantly improved at 3 days and 12 months after the surgery in each group (p 0.05), but no significant statistical difference was found at each time point between the groups (p 0.05). No pulmonary embolism, neurovascular injury, and infection occurred. No significant difference was found in fracture recurrence rate within 12 months after operation (p 0.05). Conclusion: Unilateral extrapedicular percutaneous kyphoplasty is an effective and safe way in treating thoracolumbar osteoporotic fractures with relatively less duration of surgery, intraoperative X-ray exposure, bone cement volume, and leakage rate.