Objectives: The general consensus is that surgical treatment is advised when conservative methods fail in patients with lumbosacral radicular syndrome (LRS). Preliminary evidence from our pilot study indicates that combination therapy (mechanical diagnosis therapy and transforaminal epidural injections) can prevent surgical treatment in patients on the waiting list for surgery. The pilot study lacked a control group, and therefore, firm conclusions pertaining to effects could not be made. This study aims to determine if combination therapy, performed while being on the waiting list for lumbar herniated disc surgery, is effective and cost-effective compared with usual care (i.e., no intervention while being on the waiting list) among patients with a magnetic resonance imaging (MRI)-confirmed indication for a lumbar herniated disc surgery. Methods: A randomized controlled trial will be conducted with an economic evaluation. Patients aged 18 and above with incapacitating LRS, with leg pain and an MRI confirmed indication for lumbar disc hernia surgery, will be recruited from seven Dutch hospitals. While being on the waiting list for lumbar herniated disc surgery, patients will be randomized to either the combination therapy or usual care group. The primary outcome measure is the number of patients undergoing lumbar disc surgery during 12-month follow-up. Secondary outcomes include back and leg pain intensity (numeric pain rating scale), physical functioning (Roland Morris Disability Questionnaires-23), self-perceived recovery (global perceived effect), and health-related quality of life (EuroQol Five Dimensions Health Questionnaire (EQ-5D-5L) and 12-Item Short Form Health Survey (SF-12)). For the economic evaluation, societal and health care costs will be measured. Measurements moments are baseline, 1, 2, 4, 6, 9, and 12 months. Data will be analysed according to the intention-to-treat principle. Conclusion: No randomized controlled trials have evaluated the effectiveness and cost-effectiveness of combination therapy compared with usual care in patients with an indication for lumbar herniated disc surgery, which emphasizes the importance of this study.