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Objectives The operative microscope (OM) has revolutionized the field of modern spine surgery, however, it remains limited by several drawbacks. Recently, the exoscope (EX) system has been designed to assistant spine surgery. It provides a three‐dimensional (3D) high‐definition (HD) operative experience and becomes an alternative to the OM. The aim of the study was to evaluate the clinical outcomes, advantages and limitations of EX‐assisted minimally invasive transforaminal lumbar interbody fusion (EMIS‐TLIF) and OM‐assisted MIS‐TLIF (OMIS‐TLIF). Methods The clinical outcomes were assessed in 47 patients with lumbar degenerative diseases (LDD) who underwent MIS‐TLIF assisted with the OM or EX between January 2019 and September 2020. A total of 22 were treated with EMIS‐TLIF, and 25 received OMIS‐TLIF. Perioperative parameters (including sex, age, number of fusion levels and body mass index), perioperative parameters (operation time, intraoperative blood loss, postoperative drainage, postoperative hospitalization stay, and duration of follow‐up), visual analogue scale (VAS) of back pain, VAS of leg pain, Oswestry disability index (ODI) scores and clinical outcomes were assessed and compared. Image quality, handling of equipment, ergonomics, 3D glasses and educational usefulness were scored according to a questionnaire. Results Operation time in the OMIS‐TLIF group (121.92 ± 16.92 min) was significantly increased compared with that in the EMIS‐TLIF group (111.00 ± 19.87 min) (P