Background: Comparative outcomes of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) and traditional open TLIF (O-TLIF) for degenerative lumbar disc disease have been poorly studied. The purpose of this study was to prospectively compare the outcomes between MI-TLIF and O-TLIF for patients with a degenerative disc disease, focusing on the functional capacity of patients in daily life. Methods: A prospective cohort study was performed, comparing 54 patients who underwent O-TLIF and 55 patients who underwent MI-TLIF with a follow-up of 4 years. Clinical evaluation was performed using the Oswestry Disability Index (ODI), 36-item short form survey (SF-36), and a visual analog scale for pain (VAS pain). Radiological evaluation was also performed. Results: At the final follow-up, compared with O-TLIF, MI-TLIF was associated with significantly better intraoperative results, including similar operative time (p = 0.246), lower estimated blood loss (p = 0.001), and shorter hospital stay (p = 0.001). The final ODI score was significantly better in the MI-TLIF group (p = 0.031). The SF-36-physical (p = 0.023) and VAS pain (p = 0.024) scores were significantly better in the MI-TLIF group. There was no significant difference in the fusion rate (p = 0.747). Conclusions The MI-TLIF technique is an effective and safe procedure for degenerative lumbar disc disease. Compared to traditional O-TLIF, MI-TLIF was associated with less disability and higher quality of life, with a low rate of intraoperative and postoperative complications.