Screw loosening (SL) is a common complication following lumbar interbody fusion (LIF), particularly for degenerative lumbar disease. This study investigated the risk factors for SL following LIF for degenerative lumbar disease and examined the clinical relevance of SL. A PROSPERO-registered systematic search was conducted in the ScienceDirect, PubMed, Google Scholar, Epistemonikos, and Cochrane databases to identify longitudinal studies up to October 2024. Degenerative lumbar diseases included stenosis, spondylolisthesis, and disc herniation. Assessed risk factors were Cobb angle, lumbar lordosis (LL) angle, screw length, fixation to the sacrum, fused levels, and Hounsfield units (HU). Twenty-two studies involving 3,689 participants (56%±5% female; mean age, 61.95±9.55 years) and 17,722 lumbar screws were analyzed. Overall, 10%±2% of screws exhibited loosening in 29%±5% of patients, with 5%±2% undergoing revision surgery. Patients with SL (SL group) and those without SL (non-SL group) had similar sex distribution, body mass index, and comorbidities. The SL group had higher Visual Analog Scale scores for back pain (mean difference [MD], 0.75; 95% confidence interval [CI], 0.42–1.07; p<0.001) and Oswestry Disability Index scores (MD, 3.34; 95% CI, 0.49–6.20; p=0.02), indicating the clinical relevance of SL. The SL group exhibited significantly higher Cobb angle (MD, 2.42; 95% CI, 0.36–4.49; p=0.02), lower LL angle (MD, −3.67; 95% CI, −6.33 to −1.01; p=0.01), and shorter screw length (MD, −1.62; 95% CI, −2.78 to −0.45; p=0.01). Fixation to the sacrum, increased fused levels, and decreased HU were significant risk factors. The area under the curve for HU was 0.80 (0.77–0.84), with a sensitivity of 0.74 (0.67–0.81) and specificity of 0.76 (0.66–0.84), underscoring notable prognostic value. Patients with SL exhibited higher Cobb angles, lower LL angles, and shorter screws. Fixation to sacrum, increased fused levels, and decreased HU were significant risk factors for SL (PROSPERO ID: CRD42024563780).