54 randomized controlled trials were included in this meta-analysis evaluating the efficacy of intra-articular hyaluronic acid (IAHA) injections versus intra-articular placebo in the treatment of knee osteoarthritis. The pooled analysis of the change in pain scores significantly favoured IAHA over IA placebo at 4, 8, 12, 16, 20 and 24 weeks. The function and stiffness results favoured IAHA at 4 weeks, though effect sizes thereafter decreased markedly. The meta-regression analysis identified blinding practices, trial size, and molecular weight of HA products as possible factors that influenced pooled estimates of effect size.