Background: Adjacent segment disease (ASD) is a well-known complication after interbody fusion. Pedicle screwrod revision possesses sufficient strength and rigidity. However, is a surgical segment with rigid fixation necessary for ASD reoperation? This study aimed to investigate the biomechanical effect of different instrumentation on lateral lumbar interbody fusion (LLIF) for ASD treatment. Methods: A validated L2~5 finite element (FE) model was modified for simulation. ASD was considered the level cranial to the upper-instrumented segment (L3/4). Bone graft fusion in LLIF with bilateral pedicle screw (BPS) fixation occurred at L4/5. The ASD segment for each group underwent a) LLIF + posterior extension of BPS, b) PLIF + posterior extension of BPS, c) LLIF + lateral screw, and d) stand-alone LLIF. The L3/4 range of motion (ROM), interbody cage stress and strain, screw-bone interface stress, cage-endplate interface stress, and L2/3 nucleus pulposus of intradiscal pressure (NP-IDP) analysis were calculated for comparisons among the four models. Results: All reconstructive models displayed decreased motion at L3/4. Under each loading condition, the difference was not significant between models a and b, which provided the maximum ROM reduction (73.8 to 97.7% and 68.3 to 98.4%, respectively). Model c also provided a significant ROM reduction (64.9 to 77.5%). Model d provided a minimal restriction of the ROM (18.3 to 90.1%), which exceeded that of model a by 13.1 times for flexion-extension, 10.3 times for lateral bending and 4.8 times for rotation. Model b generated greater cage stress than other models, particularly for flexion. The maximum displacement of the cage and the peak stress of the cageendplate interface were found to be the highest in model d under all loading conditions. For the screw-bone interface, the stress was much greater with lateral instrumentation than with posterior instrumentation.