Abstract: Objective To assess the therapeutic effect of hyaluronate acid (HA) injection through the subpatellar route for treatment of chondromalacia patellae (CP). Methods Eighty-eight patients with the diagnosis of CP were enrolled in this prospective study, including 38 with early CP (CP group) and 50 with advanced CP (patellofemoral arthritis group) diagnosed based on image presentations. All the patients received intra-articular HA injections through a subpatellar route once a week for 5 consecutive weeks. The primary outcome measures included WOMAC index scores and Lequesne scores before and at 4, 12, 26 and 52 weeks after the injections. The secondary outcome measures included the 30-m walking time and stair ascending and descending time (one floor) before and at 1, 2, 3, and 4 weeks after the injections. Results In both groups the patients showed significantly decreased WOMAC scores and Lequesne scores at 4, 12, 26 and 52 weeks after HA injections as compared with the baseline scores (all P<0.01). No significant difference was found between the two groups in WOMAC scores and Lequesne scores at 4 or 12 weeks after the injections (both P>0.05). The WOMAC scores and Lequesne scores at 26 and 52 weeks after the injections were significantly higher in patellofemoral arthritis group than in CP group (both P<0.05). In both groups, the 30-m walking time and the stair ascending and descending time decreased significantly at 1, 2, 3, and 4 weeks after HA injections (all P<0.05) without significant differences between the two groups (all P>0.05). Conclusion HA injection through the subpatellar route is effective for treatment of CP. HA injection produces better long-term efficacy for treatment of early CP than for advanced CP where patellofemoral arthritis occurs.