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Lumbar midline interlaminar and transforaminal (TF) epidural steroid injections are treatments for low back pain with radiculopathy secondary to degenerative disk disease. Since pain generators are located anteriorly in the epidural space, ventral epidural spread is the logical target for placement of antiinflammatory medications. In this randomized, prospective, observational study, we compared contrast flow patterns in the epidural space using the parasagittal interlaminar (PIL) and transforaminal approaches with continual fluoroscopic guidance.Sixty adult patients with low back pain and unilateral radiculopathy from herniated or degenerated discs were enrolled. Subjects were randomly assigned to one of two groups: TF or PIL (30 in each). All procedures were performed using continual fluoroscopic guidance and 5 mL of contrast. Contrast spread was rated (primary outcome measure) by the interventionalist. Spread was scored 0–2, with 0 = no anterior spread; 1 = anterior spread, same level as needle insertion; and 2 = anterior spread at ≥1 segmental level. The secondary outcome measure was analgesia at 2 wk, 1, 3, and 6 mo.One hundred percent (29 of 29) patients in the PIL group and 75% (21 of 28) patients in the TF group demonstrated anterior epidural spread. The mean spread grade was 1.93 (95% confidence interval [CI], 1.83–2.0) in the PIL group and 1.46 (95% CI, 1.17–1.46) in the TF group (P = 0.003). Mean fluoroscopy time was 28.96 s (95% CI, 23.9–34.1 s) in the PIL group and 46.25 s (95% CI, 36.27–56.23 s) in the TF group (P = 0.003). Visual analog scale scores were equivalent between groups.The PIL approach is superior to the TF approach for placing contrast into the anterior epidural space with reduction in fluoroscopy times and an improved spread grade. With increasing attention to neurological injury associated with TF, the PIL approach may be more suitable for routine use.