The current study evaluated 40 studies, 20 which evaluated basic science differences in intra-articular hyaluronic acid (IA-HA) products, while 20 examined assessments of clinical outcome differences between IA-HA product differences. Basic science evaluations found that molecular weight of IA-HA products had an impact on cellular response in the knee joint, which demonstrated differences in anti-inflammatory, chondroprotective, proteoglycan synthesis, analgesic, and subchondral effects. High-molecular weight hyaluronic acid (HMW-HA) products are suggested to demonstrate a better biological and rheological response in knee osteoarthritis, and the results of several meta-analyses examining product differences on clinical outcomes support this conclusion.