Background: Radiological evidence of adjacent segment disease (ASD) has been reported to have a prevalence of more than 30% and several risk factors have been reported. The aim of this study is to evaluate the clinical and radiological outcomes of patients with symptomatic ASD treated with stand-alone OLIF and compare results with a posterior revision surgery cohort. Methods: This is a retrospective case-control study. Clinical-patient-reported outcomes were obtained at preoperative, postoperative and final follow-up visits using the Short Form (SF-36) scale, the Oswestry Disability Index (ODI) and the visual analog scale (VAS). Radiological measures include lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence-lumbar lordosis (PI-LL) mismatch, segmental coronal Cobb angle and intervertebral disc height (DH). The data are compared with a retrospective series of patients that underwent a posterior revision surgery for ASD. Results: Twenty-eight patients in the OLIF group and 25 patients in the posterior group meet inclusion criteria. The mean ages at the time of the surgery are 65.1 years and 67.5, respectively. The mean follow-up time is 36.1 months (range of 14-56). The clinical outcomes significantly improve from preoperative values from the surgery in both groups. The radiological parameters are significantly improved postoperatively and were maintained at the last follow-up in both groups. A statistically significant difference is observed between the two groups for minor complication rate, length of surgery, blood loss and DH restoration. Conclusions: Stand-alone OLIF is an effective and safe technique with low morbidity and complication rates for the treatment of selected patients with symptomatic ASD following a previous lumbar fusion.