BackgroundThe number of patients operated on for total knee arthroplasty (TKA) is growing worldwide. Outpatient surgery is defined by a length of stay (LOS) in the hospital of less than 12 h. This can be limited for TKA, with the efficient management of pain and perioperative complications, such as blood loss, affecting a safe hospital discharge. Outpatient TKA with a suitable protocol, including multimodal measures, could improve the success rate of this procedure. Among the main measures, single-shot sciatic nerve block in association with continuous femoral nerve block for pain control needs to be evaluated in outpatient TKA. Furthermore, to promote the safety of the postoperative period and to accelerate rehabilitation, patients who undergo ambulatory TKA could be discharged to a rehabilitation center on the day of surgery to screen adverse events and to optimize the rehabilitation process. This study is designed to assess the benefits of sciatic nerve block in postoperative pain relief for outpatient TKA.Methods/designThis randomized prospective controlled study will be conducted in the knee unit of the teaching hospital of the Nice university and will include 40 patients undergoing primary unilateral outpatient TKA, discharged the day of surgery to a private rehabilitation center for enhanced recovery after surgery, after a hospital stay of less than 12 h. Before surgery, all patients will receive a continuous femoral nerve block with 2 mg/ml ropivacaine 20 ml, and then patients will be randomly assigned to receive or not receive a single-shot sciatic nerve block with 2 mg/ml ropivacaine, 20 ml. The primary outcome measure is the success rate of outpatient TKA. This rate is defined by patients discharged from the hospital to a rehabilitation center the day of surgery with no re-hospitalization due to insufficient pain control before the fifth postoperative day. Secondary outcomes include the incidence of major and minor adverse events during the first five postoperative days and measurement of the quality of recovery using the Knee injury and Osteoarthritis Outcome Score and the new International Knee Society scores plus the Quality of Recovery-40 questionnaire.DiscussionThe assessment of anesthesia and rehabilitation protocols enabling major orthopedic surgery, such as TKA, is necessary. This randomized controlled study will address the hypothesis that a suitable multimodal protocol including sciatic nerve block could improve pain control and thus improve the success rate of outpatient TKA.Trial registrationEudraCT, 2016-000226-19. Registered on 15 April 2016.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3142-1) contains supplementary material, which is available to authorized users.