Background:Piriformis Syndrome (PS) is an underdiagnosed cause of buttock, thigh and leg pain, most probably because it is thought to be a rare cause of sciatica. PS is widely believed to be myofascial in origin.Materials and Methods:This prospective, randomized, controlled, double-blind study was conducted at the pain management department. 50 patients aged from 20 to 60 years old were included in this study. The selected patients were randomly allocated into 2 groups containing 25 patients each; Group D received a total of 5 mL which included 2mL lidocaine 2%, 2mL (8 mg) dexamethasone and 1mL normal saline 0.9%, and Group M received a total of 5mL which included 2mL lidocaine 2%, 3mL magnesium sulphate (MgSO4) (2.5%) . Patients demographic characteristics, baseline physical examination findings of the patients as well as the duration of pain were all recorded. Patients were re-assessed immediately after injection, 1 week, 1 month, and 3 months after the injection. Numeric Rating Scale (NRS) values were used at each evaluation time to assess the pain, while patients were in sitting, standing, and lying positions. All patients were assessed immediately and for 4 hours post-injection for any side effects related to the drugs used.Results:In the pre-injection time, immediately after and 1 week after injection, there were no statistically significant differences between groups D and M in pain values. While, on comparison between both groups, group M, was significantly better than group D, in NRS values 1 month and 3 months after injection. In group D, pain score values were significantly better immediately, 1 week, and 1 month after injection compared to the pre-injection values, while these values were not significantly different 3 months after injection compared with the pre-injection values. In group M, pain score values were significantly better immediately, 1 week, 1 month, and 3 months after injection compared to the pre-injection values.Conclusion:Magnesium sulfate was more effective, especially for long term pain relief (3 months) when compared to dexamethasone as they were used as adjuvants to lidocaine, if injected into the piriformis muscle (PM) guided by ultrasound in the management of PS refractory as initial conservative treatment.