INTRODUCTION: Does lumbar fusion lead to accelerated adjacent segment disc degeneration (ASDD) or is it explained by genetics and aging? The influence of genetics on ASDD remains to be explored. This study assesses whether the disc space height adjacent to a fused segment is associated with candidate gene single nucleotide polymorphisms (SNPs). METHODS: European patients with low back pain from 4 RCTs (N=208 had fusion; 77, non‐operative treatment) underwent standing plain radiography and genetic analyses at 13±4 years follow‐up. Disc space height was measured using a validated computer‐assisted distortion compensated roentgen analysis technique and reported in standard deviations from age and gender adjusted normal values. Genetic association analyses included 34 SNPs in 25 genes relevant to disc degeneration. Analyses were adjusted for age, gender, smoking, duration of follow‐up, and treatment group. RESULTS: Decreased disc space height at the adjacent level was associated with age (β= ‐0.05, p= < 0.001) and two SNPs (rs1420106 and rs917997) from the IL18RAP gene (β= ‐0.34, p= 0.04 and β= ‐0.35, p= 0.04, respectively); together, these explained 11% of the variance. Fusion was also significantly associated with decreased disc space height (β= ‐0.50, p= < 0.008), explaining a further 2‐3% variance. rs20544 from the MMP‐9 gene was associated with greater disc space height (β= 0.35, p= 0.04) and, together with age and fusion, explained 14% variance. No associations were observed for the haplotypes tested. At the 2 levels above the adjacent segment, two SNPs from IL6 gene were associated with greater disc space height and SNPs from IL18RAP, COX2 and CILP genes with lower height. DISCUSSION: Age was the most significant determinant of disc space height; genetic factors, specifically inflammatory genes, and fusion explained a statistically significant but small proportion of the variance. Gene‐environment interactions may be important to consider in future studies.