The purpose of this systematic review and meta-analysis was to determine whether epidural steroid injections (ESI) are superior to epidural or non-epidural placebo injections in sciatica patients. The PubMed, Embase, Cochrane Library, and Web of science databases were searched for trials comparing ESI to epidural or non-epidural placebo. Risk of bias was assessed using the Cochrane RoB 2 tool. The primary outcome measures were pooled using a random-effects model for 6-week, 3-month, and 6-month follow-up. Secondary outcomes were described qualitatively. Quality of evidence was graded using GRADE classification. Seventeen out of 732 articles were included. ESI was superior compared to epidural placebo at 6 weeks (− 8.6 [− 13.4; − 3.9]) and 3 months (− 5.2 [− 10.1; − 0.2]) for leg pain and at 6 weeks for functional status (− 4.1 [− 6.5; − 1.6]), though the minimally clinical important difference (MCID) was not met. There was no difference in ESI and placebo for back pain, except for non-epidural placebo at 3 months (6.9 [1.3; 12.5]). Proportions of treatment success were not different. ESI reduced analgesic intake in some studies and complication rates are low. The literature indicates that ESI induces larger improvements in pain and disability on the short term compared to epidural placebo, though evidence is of low to moderate quality and MCID is not met. Strong conclusions for longer follow-up or for comparisons with non-epidural placebo cannot be drawn due to general low quality of evidence and limited number of studies. Epidural injections can be considered a safe therapy.