BackgroundPercutaneous kyphoplasty (PKP) has become a mainstream intervention for osteoporotic vertebral compression fractures (OVCFs). While existing systematic reviews comparing unilateral and bilateral PKP approaches provide preliminary insights, they are limited by methodological inconsistencies and inconclusive evidence regarding comparative efficacy.MethodsWe conducted a comprehensive systematic review of randomized controlled trials (RCTs) up to July 2024, searching major English databases (Cochrane Library, Embase, PubMed, Scopus, Web of Science) and Chinese databases (CNKI, VIP, and Wanfang).ResultsThe pooled analysis of 35 RCTs (N = 3,362) revealed no statistically significant differences between unilateral and bilateral PKP in long-term outcomes, including visual analog scale scores (P = 0.62), Oswestry Disability Index scores (P = 0.77), and Cobb angle correction (P = 0.64). However, unilateral PKP demonstrated significant perioperative advantages: shorter operative time (P