Objective To compare the short-term effectiveness of minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF) versus open-TLIF in treatment of single-level lumbar degenerative disease. Methods Between February 2010 and February 2011, 147 patients with single-level lumbar degenerative diseases underwent open-TLIF in 104 cases (open-TLIF group) and MIS-TLIF in 43 cases (MIS-TLIF group), and the clinical data were analyzed retrospectively. There was no significant difference in gender, age, disease type, lesion level, disease duration, preoperative visual analogue scale (VAS), and preoperative Oswestry disability index (ODI) between 2 groups (P gt; 0.05). The operation time, intraoperative radiological exposure time, intra- and post-operative blood loss, postoperative hospitalization time, and postoperative complications were compared between 2 groups. The VAS score and ODI were observed during follow-up. The imaging examination was done to observe the bone graft fusion and the locations of internal fixator and Cage. Results There was no significant difference in operation time between 2 groups (t=0.402, P=0.688); MIS-TLIF group had a decreased intra- and post-operative blood loss, shortened postoperative hospitalization time, and increased intraoperative radiological exposure time, showing significant differences when compared with open-TLIF group (P lt; 0.05). Cerebrospinal fluid leakage (2 cases) and superficial infection of incision (2 cases) occurred after operation in open-TLIF group, with a complication incidence of 3.8% (4/104); dorsal root ganglion stimulation symptom (3 cases) occurred in MIS-TLIF group, with a complication incidence of 7.0% (3/43); there was no significant difference in the complication incidence between 2 groups (χ2=0.657, P=0.417). The patients were followed up 18-26 months (mean, 21 months) in MIS-TLIF group, and 18-28 months (mean, 23 months) in open-TLIF group. The VAS scores and ODI of 2 groups at each time point after operation were significantly improved when compared with those before operation (P lt; 0.05). There was no significant difference in VAS score between 2 groups at discharge and 3 months after operation (P gt; 0.05); VAS score of MIS-TLIF group was significantly lower than that of open-TLIF group at last follow-up (t= — 2.022, P=0.047). At 3 months and last follow-up, no significant difference was found in the ODI between 2 groups (P gt; 0.05). The imaging examination showed good positions of Cage and internal fixator, and bone graft fusion in 2 groups. Conclusion The short-term effectiveness of MIS-TLIF and open-TLIF for single-level degenerative lumbar diseases was similar. MIS-TLIF has the advantages of less invasion and quick recovery, but the long-term effectiveness needs more observation.