We sought to determine the clinical outcomes, complications, and fusion rates in transiliac endoscopic-assisted L5S1 intraforaminal lumbar interbody fusion (iLIF). Between September 2020 and September 2021, patients with L5S1 degenerative disk disease were enrolled in a prospective study on transiliac L5S1 iLIF and followed for a minimum of 12 months. Conflict of the preoperative planned approach with the ilium was mandatory. The primary outcome measures were the Oswestry Disability Index, the visual analog scale (VAS) score for low back pain (VAS back) and leg pain (VAS leg), and the modified MacNab criteria. The secondary outcomes were complications and fusion rates. Five consecutive patients were enrolled: 2 males and 3 females with a mean age of 50 ± 12.9. All had 12 months' follow-up. The mean improvement in the Oswestry Disability Index, VAS back, and VAS leg (44 ± 11.75, 6.6 ± 1.7, and 4.7 ± 4.2, respectively) was more than 3 times the minimum clinically important difference. The modified MacNab criteria were good or excellent in 80% of cases at all endpoints. Three patients had ipsilateral lower limb dysesthesia. One patient had revision surgery for foraminal bone fragment removal. All patients achieved fusion. The transiliac iLIF is a feasible but demanding surgical technique that allows overcoming cases in which the ilium prevents endoscopic transforaminal access to L5S1. Our preliminary results had good clinical outcomes and high fusion rates. The main complication was late-onset dysesthesia of the ipsilateral lower limb, 10 to 14 days after surgery. Special care must be taken to prevent L5 dorsal root ganglion injury.