In this paper the authors evaluate through in vitro biomechanical testing the performance of an interspinous fusion device as a stand-alone device, after lumbar decompression surgery, and as supplemental fixation to expandable cages in a posterior lumbar interbody fusion (PLIF) construct. Nine L3-4 human cadaveric spines were biomechanically tested under the following conditions: 1) intact/control; 2) L3-4 left hemilaminotomy with partial discectomy (injury); 3) interspinous spacer (ISS); 4) bilateral pedicle screw system (BPSS); 5) bilateral hemilaminectomy, discectomy, and expandable posterior interbody cages with ISS (PLIF-ISS); and 6) PLIF-BPSS. Each test consisted of 100 N of axial preload with ± 7.5 Nm of torque in flexion-extension, right/left lateral bending, and right/left axial rotation. Significant changes in range of motion (ROM), neutral zone stiffness (NZS), elastic zone stiffness (EZS), and energy loss (EL) were explored among conditions using nonparametric Friedman test and Wilcoxon signed-rank comparisons (p ≤ 0.05). The injury increased ROM in flexion (p = 0.01), left bending (p = 0.03), and right/left rotation (p < 0.01) and also decreased NZS in flexion (p = 0.01) and extension (p < 0.01). Both the ISS and BPSS reduced flexion-extension ROM and increased flexion-extension stiffness (NZS and EZS) with respect to the injury and intact conditions (p < 0.05), but the ISS condition provided greater resistance than BPSS in extension for ROM, NZS, and EZS (p < 0.01). The BPSS increased the rigidity (ROM, NZS, and EZS) of the intact model in lateral bending and axial rotation (p ≤ 0.01), except in EZS for left rotation (p = 0.23, Friedman test). The incorporation of posterior cages marginally increased (p = 0.05) the EZS of the BPSS construct in flexion but these interbody devices provided significant stability to the ISS construct in lateral bending and axial rotation for ROM (p = 0.02), in lateral bending for NZS (p = 0.02), and in flexion/axial rotation for EZS (p ≤ 0.03); however, both PLIF constructs demonstrated equivalent ROM and stiffness (p ≥ 0.16), except in lateral bending where the PLIF-BPSS was more stable (p = 0.02). In terms of EL, the injury increased EL in flexion-extension (p = 0.02), the ISS increased EL for lateral bending and axial rotation (p ≤ 0.03), and the BPSS decreased EL in lateral bending (p = 0.02), with respect to the intact condition. The PLIF-ISS decreased lateral bending EL with respect to the ISS condition (p = 0.02), but not enough to be smaller or, at least, equivalent, to that of the PLIF-BPSS construct (p = 0.02). The ISS may be a suitable device to provide immediate flexion-extension balance after a unilateral laminotomy, but the BPSS provides greater immediate stability in lateral bending and axial rotation motions. Both PLIF constructs performed equivalently in flexion-extension and axial rotation, but the PLIF-BPSS construct is more resistant to lateral bending motions. Further biomechanical and clinical evidence is required to strongly support the recommendation of a stand-alone interspinous fusion device or as supplemental fixation to expandable posterior interbody cages.