Background: While all surgical procedures are associated with some degree of pain, it is a well-accepted fact that orthopedic surgeries are some of the most painful. Despite the increasing interest and continuous advancement in postoperative pain management, more than half of the patients who undergo orthopedic surgeries experience inappropriate level of postoperative pain. Poorly treated pain can have negative impact on recovery especially owing to disruption in physiotherapy resulting in stiffness of joints and slow progress in mobility. In order to achieve good quality of postoperative analgesia, careful history should be taken from the patients about any coexisting medical conditions such as substance abuse or withdrawal, anxiety disorder, affective disorder, hepatic or renal impairment and any past history of poor pain management. Aim of the Work: The purpose of this study was to compare efficacy, side effects, opiate consumption and hemodynamic effects of neuraxial blocks versus peripheral nerves blocks placed under ultrasound guidance, for postoperative pain management in drug abusers undergoing orthopedic surgeries. Patients and Methods: Sixty patients presenting to Ain Shams University hospitals for orthopedic surgeries were enrolled in this prospective randomized controlled study after providing written consents. Participants were instructed about the study protocol and visual analogue scale (VAS). Approval was obtained from the research ethics committee of anesthesia and intensive care department, at Ain Shams University. In this study, all patients were preoperatively assessed for evaluation of their medical status, mode of trauma, post-traumatic critical symptoms or signs, hemodynamic stability, evidence of coagulopathy and any previous history or concurrent drug abuse. Results: This study included 60 drug-abuser patients, undergoing orthopaedic surgeries, starting from January 2018 till May 2018 at Ain Shams University Hospitals and randomly distributed within 2 groups, 30 patients each: Group A: EPI group, Group B: PNB group. As regard to age, gender, body weight, height, ASA and duration of surgery, there were no statistically significant differences between both groups (P-value>0.05). Regarding effects on hemodynamics and intraoperative ephedrine administration, the present study found statistically significant difference in the mean arterial blood pressure measured intra operatively with more drop in group A (EPI) than group B (PNB) with a (P value < 0.001). Also there was significant increase in heart rate from baseline readings in group A compared to group B (P value < 0.001). Statistically significant more incidence of intraoperative ephedrine administration was found in group A compared to group B with a (P value < 0.001). Regarding incidence of postoperative side effects such as sedation, dizziness, nausea, vomiting and urine retention, there was statistically significant more incidence in group A (EPI) than group B (PNB) with a (P value < 0.001). Regarding postoperative pain assessment using VAS, opioids consumption, fulfillment of rehabilitation programs and hospital stay, there were no statistically significant differences between both groups (P value > 0.05). Conclusion: The choice of continuous femoral and sciatic block technique placed under ultra-sound guidance for postoperative pain control provides equivalent analgesia, opioid consumption, postoperative rehabilitation and hospital stay with a lower incidence of hemodynamic side effects when compared to continuous epidural analgesia in drug-abuser patients undergoing orthopedic surgeries. It was also associated with decreased risk of postoperative side effects as sedation, dizziness, nausea and\or vomiting and urinary retention.