Background and Objectives: This pilot study aimed to evaluate the clinical effectiveness, cost-effectiveness, and safety of acupotomy combined with epidural steroid injection (ESI) in lumbosacral radiculopathy and examine its feasibility for the main study. Materials and Methods: This randomized, controlled, two-arm, parallel, assessor-blinded, pragmatic study included 50 patients with severe lumbosacral radiculopathy who had insufficient improvement after an ESI. Patients were randomized (1:1 ratio) into a combined treatment (acupotomy + ESI, experimental) and an ESI single treatment (control) group. Both groups underwent a total of two ESIs once every 2 weeks; the experimental group received eight additional acupotomy treatments twice a week for 4 weeks. Types of ESI included interlaminar, transforaminal, and caudal approaches. Drugs used in ESI comprised a 5–10 mL mixture of dexamethasone sodium phosphate (2.5 mg), mepivacaine (0.3%), and hyaluronidase (1500 IU). The primary outcome was the difference in changes from baseline in the Oswestry Disability Index (ODI) scores between the groups at weeks 4 and 8. The incremental cost-utility ratio (ICUR) was calculated to evaluate the cost-effectiveness between the groups. Adverse events (AEs) were assessed at all visits. Results: Mean ODI scores for the experimental and control groups were −9.44 (95% confidence interval [CI]: −12.71, −6.17) and −2.16 (95% CI: −5.01, 0.69) at week 4, and −9.04 (95% CI: −12.09, −5.99) and −4.76 (95% CI: −7.68, −1.84) at week 8, respectively. The difference in ODI score changes was significant between the groups at week 4 (p = 0.0021). The ICUR of the experimental group versus the control group was as economical as 18,267,754 won/quality-adjusted life years. No serious AEs were observed. Conclusions: These results demonstrate the potential clinical effectiveness and cost-effectiveness of acupotomy combined with ESI for lumbosacral radiculopathy and its feasibility for a full-scale study. Larger, long-term follow-up clinical trials are needed to confirm these findings.