Through this single-center consecutive prospective study, we evaluated the results of a combined approach for L5-S1 isthmic spondylolisthesis, using a polyetheretherketone (PEEK) interbody lordotic cage during anterior approach and pedicle screw-based posterior fixation. Between 2010 and 2014, 27 adult patients were treated for L5-S1 isthmic spondylolisthesis (high and low grades) by a combined approach with a minimum follow-up of one year. Clinical outcome was assessed before surgical treatment and at four months and one year after surgery by: VAS, Oswestry Index (ODI) and Rolland-Morris scores. Two observers evaluated the following radiological parameters: pelvic incidence, pelvic tilt, lumbar lordosis, segmental lordosis L5-S1, anterior and posterior disc height, spinal vertical axis (SVA), SVA/sacro-femoral distance (SFD) ratio. Fusion was evaluated on the CT scan at one-year follow-up. Blood loss, surgery time and complications were also collected. The mean age was 47.7 years (±16.9). The VAS, ODI and Rolland-Morris scores were significantly improved postoperatively, decreased from 7.5 (±1.45); 48 (±19.25); 15.3 (±4.67) before the surgery to 3.8 (±2.55); 28.7 (±19.58) and 7.76 (±7.21) respectively at one year after the surgery (P=0.05). The mean follow-up was 3.3 years. Mean surgery time was 193.7min (±37). Fusion was obtained in 100% of cases. Segmental lordosis L5-S1, pelvic tilt, slippage, anterior and posterior L5-S1 disc height were significantly improved postoperatively, they passed from 20.1; 22.6; 35.3%; 26.4%; 17.9% to 29.5; 20.6; 20.3%; 64.4%; 36.3% respectively. Combined surgical procedure meets the required goals of surgery in the treatment of adults L5-S1 isthmic spondylolisthesis.