Objective. Discectomy remains the classic procedure for treating lumbar intervertebral disc (IVD) herniation, but the occurrence of defects after discectomy is thought to be an important cause generating recurrent and accelerated IVD degeneration. Previous studies attempted suture of the annulus fissure, but the validity of this technique on restraining the degenerative process is controversial. On the other hand, cell therapies have been shown in multiple clinical and basic studies. Our purpose was to investigate the effectiveness of selective retention of autologous Bone Marrow Stromal Cells (BMSCs) with gelatin sponge in combination with annulus fibrosus suture (AFS) for the repair of IVD defects following mobile microendoscopic discectomy (MMED). Methods. This prospective, two-armed, and controlled clinical study was conducted from December 2016 to December 2018. Written informed consent was obtained from each patient. Forty-five patients with typical symptoms, positive signs of radiculopathy, and obvious lumbar disc herniation observed by MRI were enrolled. Patients were divided into 3 groups with different treating methods: MMED (
n
=
15
), MMED+AFS (
n
=
15
), and MMED+AFS+BMSCs (
n
=
15
). A postoperative 2-year follow-up was performed to evaluate the patient-reported outcomes of VAS, ODI, and SF-36. The improvement rate of VAS and ODI was calculated as
latest
‐
preoperative
/
preoperative
to evaluate the therapeutic effect of the three groups. Assessment parameters included Pfirrmann grade, intervertebral disc height (IDH), and disc protrusion size (DPS), as measured by MRI to evaluate the morphological changes. Results. All patients enrolled had a postoperative follow-up at 3, 6, 12, and 24 months. VAS and ODI scores were significantly improved compared to the preoperative status in all three groups with a mean DPS reduction rate over 50%. At the final follow-up, the improvement rate of the VAS score in the MMED+AFS+BMSCs group was significantly higher than the MMED+AFS and MMED groups (
80.1
%
±
7.6
%
vs.
71.3
%
±
7.0
%
vs.
70.1
%
±
7.8
%
), while ODI improvement showed a significant change (
65.6
%
±
8.8
%
vs.
59.9
%
±
5.5
%
vs.
57.8
%
±
8.1
%
). All participants showed significant improvement in SF-36 PCS and MCS; the differences between each group were not significant. The mean IDH loss rate of the MMED+AFS+BMSCs group was also significantly lower than other groups (
−
17.2
%
±
1.3
%
vs.
−
27.6
%
±
0.7
%
vs.
−
29.3
%
±
2.2
%
). The Pfirrmann grade was aggravated in the MMED and MMED+AFS groups while maintained at the preoperative grade in the MMED+AFS+BMSCs group. No adverse events of cell transplantation or recurrence were found in all patients during the postoperative follow-up period. Conclusions. It is feasible and effective to repair lumbar IVD defects using SCR-enriched BMSCs with gelatin sponges, which warrants further study and development as a cell-based therapy for IVD repair.