BACKGROUND: Epidural injection (EI) is used to treat back or radicular pain from lumbosacral disc herniation (LDH). Although several reports have stated that the transforaminal approach in EI (TFEI) has an advantage in target specificity and yields better clinical efficacy than the interlaminar approach in EI (ILEI), other studies have indicated that the clinical efficacy of ILEI was not inferior to that of TFEI and that ILEI also has the ability to spread medication into the ventral space to a degree similar to that of TFEI. There has been controversy about whether TFEI is superior to ILEI in clinical efficacy. OBJECTIVES: This systematic review and meta-analysis aimed to investigate whether TFEI is more useful than ILEI for achieving clinical outcomes in patients with LDH. STUDY DESIGN: A systematic review and meta-analysis using a random effects model on randomized controlled studies (RCT). METHODS: A literature search was performed in MEDLINE, EMBASE, Cochrane review, and KoreaMed for studies published from January 1996 until July 2017. From those found fulfilling the search criteria, manuscripts that compared the clinical efficacy of steroids and control agents, such as local anesthetics or saline, in terms of pain control and functional improvement were included in this study. Exclusion criteria included a previous history of lumbosacral surgery, non-specific low back pain, severe spinal stenosis, and severe disc degeneration. After reviewing titles, abstracts, and the full text of 6,711 studies; 12 studies were included in the qualitative synthesis. Data including pain scores, functional scores, and follow-up period were extracted from 10 studies and analyzed using a random effects model to obtain effect size and its statistical significance. The quality and level of evidence were analyzed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: In terms of pain control, TFEI showed significantly better short-term (2 weeks to 1 month) outcomes and slightly favorable long-term (4 - 6 month) outcomes, but without significance, in comparison with ILEI. In terms of functional improvement, TFEI also showed favorable short- and long-term outcomes, but without significance, in comparison with ILEI. TFEI had target specificity, required no additional cost and resources, and had equal applicability to ILEI. However, TFEI was more associated with a higher frequency of discomfort or adverse events during the procedure. Overall, better results were reported with TFEI over ILEI, but with low-grade evidence due to the inconsistency and imprecision of the selected studies. LIMITATION: Analyses of safety or adverse effects could not be performed due to a lack of available data from the included studies. CONCLUSIONS: Based on low-grade evidence, TFEI showed significantly better short-term pain control and slightly favorable outcomes in long-term pain reduction and short- and long-term functional improvement in comparison with ILEI. KEY WORDS: Epidural injection, interlaminar, transforaminal, meta-analysis, systemic review, pain, function.