[Abstract] Objective To compare the effectiveness of ultrasound-guided ozonated water or compound betamethasone injection with single-segment puncture combined with manipulation under anesthesia (MUA) in the treatment of primary frozen shoulder (PFS). Methods A total of 100 patients with PFS who received treatment in our research center were enrolled.They were divided into group O (ozonated water) and group C (compound betamethasone) randomly.On the basis of manipulation under anesthesia, the two groups were treated with ozonated water or compound betamethasone injection respectively.The Numerical Rating Scale（NRS), active range of motion (AROM) and Activity of Daily Living (ADL) scores were recorded before treatment and 1 week, 4 weeks, 8 weeks and 12 weeks after treatment, and Self-Rating Scale of Sleep(SRSS) were recorded before treatment and 4 weeks, 8 weeks and 12 weeks after treatment. Meanwhile, the use of analgesics, adverse events and the fasting blood glucose in patients with diabetes before and after treatment were recorded. Results Compared with those before treatment, all the observed indexes in the two groups were significantly improved after treatment(P＜0.05).Compared with group C, NRS in an active state in group O increased significantly at 4 weeks after treatment(P＜0.05), but there were no statistical differences between the two groups at other time points(P＞0.05). There were no statistical differences in NRS at night, AROM, ADL and SRSS scores between the two groups after treatment(P＞0.05).The utilization of analgesics in group O was significantly higher than that in group C at 4 and 8 weeks after treatment(P＜0.05). Compared with group C, the fasting blood glucose level in group O was significantly lower than that in group C (P0.05). Conclusion The clinical effect of ultrasound-guided ozonated water injection with single-segment puncture combined with manipulation under anesthesia is slightly worse than that of compound betamethasone injection in the treatment of PFS, but it has less effect on blood glucose in patients with diabetes, so it can be used as an alternative therapy for patients with diabetes and patients with contraindications to hormone injection.