Background context: Spinal manipulation (SM) is an effective treatment for low back pain (LBP), and it has been theorized that SM induces a beneficial neurophysiological effect by stimulating mechanically sensitive neurons in the lumbar facet joint capsule (FJC). Purpose: The purpose of this study was to determine whether human lumbar FJC strains during simulated SM were different from those that occur during physiological motions. Study design/setting: Lumbar FJC strains were measured in human cadaveric spine specimens during physiological motions and simulated SM in a laboratory setting. Methods: Specimens were tested during displacement-controlled physiological motions of flexion, extension, lateral bending, and axial rotations. SM was simulated using combinations of manipulation site (L3, L4, and L5), impulse speed (5, 20, and 50 mm/s), and pre-torque magnitude (applied at T12 to simulate patient position; 0, 5, 10 Nm). FJC strains and vertebral motions (using six degrees of freedom) were measured during both loading protocols. Results: During SM, the applied loads were within the range measured during SM in vivo. Vertebral translations occurred primarily in the direction of the applied load, and were similar in magnitude regardless of manipulation site. Vertebral rotations and FJC strain magnitudes during SM were within the range that occurred during physiological motions. At a given FJC, manipulations delivered distally induced capsule strains similar in magnitude to those that occurred when the manipulation was applied proximally. Conclusions: FJC strain magnitudes during SM were within the physiological range, suggesting that SM is biomechanically safe. Successful treatment of patients with LBP using SM may not require precise segmental specificity, because the strain magnitudes at a given FJC during SM do not depend upon manipulation site.