Objective: To determine the physiologic effectiveness of multi-site, multi-depth sacral lateral branch injections. Design: Double-blind, randomized, placebo-controlled study. Setting: Outpatient pain management center. Patients: Twenty asymptomatic volunteers. Background: The dorsal innervation to the sacroiliac joint (SIJ) is from the L5 dorsal ramus and the S1-3 lateral branches. Multi-site, multi-depth lateral branch blocks were developed to compensate for the complex regional anatomy that limited the effectiveness of single-site, single-depth lateral branch injections. Interventions: Bilateral multi-site, multi-depth lateral branch green dye injections and subsequent dissection on two cadavers revealed a 91% accuracy with this technique. Session 1: 20 asymptomatic subjects had a 25-g spinal needle probe their interosseous (IO) and dorsal sacroiliac (DSI) ligaments. The inferior dorsal SIJ was entered and capsular distension with contrast medium was performed. Discomfort had to occur with each provocation maneuver and a contained arthrogram was necessary to continue in the study. Session 2: 1 week later; computer randomized, double-blind multi-site, multi-depth lateral branch blocks injections were performed. Ten subjects received active (bupivicaine 0.75%) and 10 subjects received sham (normal saline) multi-site, multi-depth lateral branch injections. Thirty minutes later, provocation testing was repeated with identical methodology used in session 1. Outcome measures: Presence or absence of pain for ligamentous probing and SIJ capsular distension. Results: Seventy percent of the active group had an insensate IO and DSI ligaments, and inferior dorsal SIJ vs 0–10% of the sham group. Twenty percent of the active vs 10% of the sham group did not feel repeat capsular distension. Six of seven subjects (86%) retained the ability to feel repeat capsular distension despite an insensate dorsal SIJ complex. Conclusion: Multi-site, multi-depth lateral branch blocks are physiologically effective at a rate of 70%. Multi-site, multi-depth lateral branch blocks do not effectively block the intra-articular portion of the SIJ. There is physiological evidence that the intra-articular portion of the SIJ is innervated from both ventral and dorsal sources. Comparative multi-site, multi-depth lateral branch blocks should be considered a potentially valuable tool to diagnose extra-articular SIJ pain and determine if lateral branch radiofrequency neurotomy may assist one with SIJ pain.