The common traditional surgical techniques for posterior lumbar interbody fusion (PLIF) and fixation are bilateral pedicle screw fixation with or without interbody cage fusion and unilateral pedicle screw fixation with ipsilateral cage fusion. However, the novel unilateral pedicle screw fixation combined with the contralateral interbody cage fusion techniquemay provide the benefits and avoid the hazards of those traditional techniques. This prospective randomized comparative clinical trial aims to compare pedicle screw fixation with contralateral interbody cage fusion and unilateral pedicle screw fixation with ipsilateral cage fusion in single-level PLIF and fixation. Methods This comparative prospective study was conducted on 60 patients subjected to a single-level PLIF and unilateral pedicle screw fixation during the period from January 2022 to July 2022 to compare two different surgical modalities: group A (unilateral pedicle screw fixation with contralateral interbody cage fusion) and group B (unilateral pedicle screw fixation with ipsilateral cage fusion). Results Operative time, blood loss, operative complications, and visual analog scale improvements showed insignificant differences between the two groups, while group A showed significant improvements in the Oswestry Disability Index and wider coronal disc heights contralateral to the screw, which is the side of the cages, during postoperative follow-up. Conclusion Unilateral pedicle screw fixation with contralateral cage fusion during the PLIF and pedicle screw fixation procedure is preferred to maintain bilateral coronal disc heights and thus better clinical and mechanical results without affection of the preceding disc.