Side effects of intra-articular hyaluronate injection include aseptic acute arthritis, which develops within hours after injection. Based on standard crystal analysis, calcium crystal shedding has been postulated to explain this complication. However, it is not known whether apatite crystals or low amounts of calcium pyrophosphate dihydrate (CPPD) crystals are also involved as to determine this requires a complete synovial fluid (SF) analysis. Two cases of such an acute arthritis are reported in patients after receiving a second Hylan GF-20 intra-articular injection. The SF did not contain CPPD, monosodium urate, or calcium apatite microcrystals as examined by microscopic analysis (using a compensated polarised light microscope) after alizarin red staining. Further studies are required to investigate possible direct proinflammatory effects of hyaluronic acid degradation products.