ObjectiveTo investigate the radiological and clinical efficacy of transforaminal lumbar bilateral interbody fusion (TLBIF) versus transforaminal lumbar unilateral interbody fusion (TLUIF) with reduction of slippage of the vertebra in isthmic lumbar spondylolisthesis (ILS). MethodsA comparative retrospective study was conducted between patients undergoing TLBIF (n = 46) and TLUIF (n = 40). Demographic data, intraoperative data, complications, and radiographic parameters, including total lumbar lordosis (LL), intervertebral disc height (IDH), and foraminal height (FH), and the final fusion rate were evaluated and compared between the two groups. Clinical outcomes were assessed by the Visual Analog Scale (VAS) for low back pain and leg pain, and the Oswestry Disability Index (ODI). ResultsSignificant improvement in terms of radiographic and clinical outcomes was achieved in both groups during the period from pre-operation to at least 24 months post-operation (all, P < 0.05). Original sentenceAnalysis of back and leg pain by VAS score and radiographic data including LL, IDH and FH showed superior improvement in TLBIF group compared with TLUIF group. However, ODI was similar between the two groups. RevisedAnalysis of radiographic data, including LL, IDH, and FH, showed superior improvement in the TLBIF group compared with the TLUIF group (all, P < 0.05). However, either back and leg pain by the VAS score or ODI was similar between the two groups (all, P > 0.05).The fusion rate was 100 % in the TLBIF group versus 95 % in the TLUIF group during the 24-month follow-up period. The operation time was longer and the complication rate was lower in the TLBIF group than in the TLUIF group (all, P < 0.05), while intraoperative blood loss was similar between the two groups (P > 0.05). ConclusionsTLBIF with reduction did not cause significant procedure-associated complications in ILS patients. The therapeutic outcome of TLBIF was satisfactory and similar to that of TLUIF for ILS. Original sentenceCompared with TLUIF, TLBIF appears to be associated with better radiological data, less postoperative back and leg discomfort, and quicker postoperative recovery. RevisedCompared with TLUIF, TLBIF appears to be associated with better radiological data, bone fusion rate, and similar patient-reported outcomes (PROs), including the ODI and VAS pain score for the back and leg.