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Lumbar interbody spacers are widely used in lumbar spinal fusion. The goal of this study is to analyze the biomechanics of a lumbar interbody spacer (Clydesdale Spinal System, Medtronic Sofamor Danek, Memphis, Tennessee, USA) inserted via oblique lumbar interbody fusion (OLIF) or direct lateral interbody fusion (DLIF) approaches, with and without posterior cortical screw and rod (CSR) or pedicle screw and rod (PSR) instrumentation. Lumbar human cadaveric specimens (L2–L5) underwent nondestructive flexibility testing in intact and instrumented conditions at L3–L4, including OLIF or DLIF, with and without CSR or PSR. OLIF alone significantly reduced range of motion (ROM) in flexion-extension (P = 0.005) but not during lateral bending or axial rotation (P ≥ 0.63). OLIF alone reduced laxity in the lax zone (LZ) during flexion-extension (P < 0.001) but did not affect the LZ during lateral bending or axial rotation (P ≥ 0.14). The stiff zone (SZ) was unaffected in all directions (P ≥ 0.88). OLIF plus posterior instrumentation (cortical, pedicle, or hybrid) reduced the mean ROM in all directions of loading but only significantly so with PSR during lateral bending (P = 0.004), without affecting the compressive stiffness (P > 0.20). The compressive stiffness with the OLIF device without any posterior instrumentation did not differ from that of the intact condition (P = 0.97). In terms of ROM, LZ, or SZ, there were no differences between OLIF and DLIF as standalone devices or OLIF and DLIF with posterior instrumentation (CSR or PSR) (P > 0.5). OLIF alone significantly reduced mobility during flexion-extension while maintaining axial compressive stiffness compared with the intact condition. Adding posterior instrumentation to the interbody spacer increased the construct stability significantly, regardless of cage insertion trajectory or screw type. [ABSTRACT FROM AUTHOR]