ObjectiveThis study aimed to compare the efficacy and safety of ultrasound-guided local injection (UGLI) of betamethasone around the shoulder and extracorporeal shock wave therapy (ESWT) in patients with hemiplegic shoulder pain. MethodForty-two patients with hemiplegic shoulder pain were randomly divided into the UGLI group (N = 21) and the ESWT group (N = 21). In the UGLI group, betamethasone was injected at the pain point around the shoulder under ultrasonic localization. In the ESWT group, an extracorporeal shock wave was performed at the pain points around the shoulder for 20 min of time, once a week, for 4 consecutive weeks. Both groups received rehabilitation training. The visual analog scale (VAS) evaluation was performed at baseline, 1 h, 1 week, and 1 month after treatment. Furthermore, Neer shoulder joint function scores, upper limb Fugl-Meyer assessment (FMA), modified Barthel index (MBI), Hamilton Depression Scale (HAMD), the MOS-item short-form health survey (SF-36) scores, and serum expression level of cytokine were evaluated at baseline and 1 month after treatment. ResultsAfter 1-h treatment, the UGLI group showed a greater effect on the degree of pain than the ESWT group (P = 0.017). After 4 consecutive weeks of intervention, the UGLI group showed a significant improvement in the serum level of cytokine expression compared with the ESWT group (P < 0.05). The range of motion (ROM) of the hemiplegic shoulder (P < 0.05) has no difference between the two groups (P > 0.05). ConclusionThe ultrasonic-guided betamethasone local injection and extracorporeal shock wave both can improve hemiplegic shoulder pain. However, the UGLI can induce a more cytokine expression level.