Introduction Lumbar interbody fusion is a surgical modality performed in selected patients with low back and radicular pain not responding to medical therapy. We aim to evaluate the main predictors of functional outcome, assessed through Oswestry Disability Index (ODI), in patients submitted to a lumbar interbody fusion. Methods A sample of 33 patients undergoing lumbar interbody fusion at a neurosurgery department between 2017 and 2020 was selected. In order to assess functional status, ODI was applied before and after surgery. Data related to patients’ medical history, current disease, and surgery performed were collected from the clinical process. Results In our cohort, functional improvement (pre-surgery ODI – post-surgery ODI) averaged 34.4 ± 23 points, suggesting robust surgical efficacy. We find patients with severe disability or worse to display relevant amelioration of their functional scores (p<0.0001), suggesting that these can benefit from lumbar interbody fusion surgery. The female gender (p=0.007) predicts a better outcome, which was surprising as no sex differences in lumbar fusion outcomes have been reported. Conversely, early symptom recurrence (p=0.015) and need for revision surgery (p=0.032) were found to be negative predictors of post-surgical functional outcome. Rapid return to the activities of daily living (p=0.001) and to work (p=0.002) was associated with post-surgical functional improvement. The underlying diagnosis that led to surgical referral and surgical modality did not affect the functional outcome in our patient cohort. Importantly, patients with previous lumbar surgeries had similar improvements to those who had never been operated on. Conclusions Severely disabled patients submitted to lumbar interbody fusion showed significant functional improvement, regardless of the referral diagnosis or the existence of previous lumbar surgeries. Additionally, sustained functional improvement resulted in a return to an active life.