The purpose of this research was to compare the efficacy and safety of unilateral versus bilateral PKP for osteoporotic vertebral compression fractures (OVCFs). Six databases (Cochrane, PubMed, MEDLINE, EMBASE, SinoMed, and CNKI) were searched without language restrictions. Twelve randomized controlled trials involving a total of 1,030 patients were identified. The results indicate that unilateral PKP had a better degree of pain relief (visual analog scale) than bilateral PKP (p ¼ 0.04; 95%CI ¼ À0.36 to À0.00) with short-term follow-up (within 4 weeks) after operation. The radiological outcome assessment with short-term follow-up after operation indicates bilateral PKP had a better degree of anterior vertebral height restoration (p ¼ 0.03; 95%CI ¼ À2.58 to À0.14). Operation time and cement dosage were less for unilateral PKP (p < 0.05). There were no differences in complications such as cement leakage and adjacent vertebral fractures between two approaches (p ¼ 0.06 and p ¼ 0.97, respectively). Life quality assessment (SF-36) indicates unilateral PKP had a better result of bodily pain relief (p < 0.05; 95%CI ¼ 3.93 to 7.48) and general health benefit (p < 0.05; 95%CI ¼ 0.02 to 2.93) with short-term follow-up after operation. We suggest that a unilateral PKP is advantageous. ß