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Abstract Purpose To determine within‐patient fusion rates of chambers filled with bioactive glass versus autologous iliac crest bone on computed tomography (CT) following anterior lumbar interbody fusion (ALIF). Methods A consecutive series of 40 patients (58 levels) that underwent single‐level (L5‐S1 only) or two‐level (L5‐S1 and L4‐L5) ALIF were assessed. Indications for fusion were one or more of the following: degenerative disc disease with or without Modic changes, spondylolisthesis, and stenosis. Each intervertebral cage had a middle beam delimiting two chambers, one of which was filled with bioactive glass and the other with autologous iliac crest bone. CT scans were graded using the Bridwell classification (grade I, best; grade IV, worst). Patients were evaluated using the Oswestry Disability Index (ODI), and by rating pain in the lower back and legs on a Visual Analog Scale (pVAS); complications and reoperations were noted. Results At 15 ± 5 months follow‐up, there were no significant differences in fusion across chambers filled with bioactive glass versus chambers filled with autologous bone (p = 0.416). Two patients with Bridwell grade III at both chambers of the L4‐L5 cages required reoperation using posterior instrumentation. Clinical assessment of the 38 remaining patients (54 levels) at 25 ± 2 months, revealed ODI of 15 ± 12, lower back pVAS of 1.4 ± 1.5 and legs pVAS of 1.9 ± 1.6. Conclusions For ALIF at L5‐S1 or L4‐L5, within‐patient fusion rates were equivalent for bioactive glass compared to autologous iliac crest bone; thus, bioactive glass can substitute autologous bone, avoiding increased operative time and blood loss, as well as donor site morbidity.