Objective Clinicians need to know whether lumbosacral radiculopathy syndrome (LRS) can be attributed to work. This review describes what work-related risk factors are associated with LRS. Methods A systematic review was performed in PubMed and Embase. Inclusion criteria were that LRS was diagnosed by a clinician and workers exposed to work-related risk factors were compared to workers less or not exposed. A quality assessment and a meta-analysis were performed, including a dose-response analysis. Results The search resulted in 7,350 references and 24 studies that fulfilled the inclusion criteria: 19 studies were rated as having a high risk of bias and 5 as having a low risk of bias. The median number of LRS patients per study were 209 (interquartile range 124-504) and the total number of participants was 10,142. The meta-analysis revealed significant associations with heavy physically demanding work (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.48-2.79), bending or twisting of the trunk (OR 2.43, 95% CI 1.67-3.55), and lifting and carrying in combination with bending or twisting of the trunk (OR 2.84, 95% CI 2.18-3.69). No significant associations were found for professional driving (OR 1.46, 95% CI 0.90-2.35) or sitting (OR 1.08, 95% CI 0.49-2.38). A dose-response relation was present per 5 years of exposure for bending (OR 1.12, 95% CI 1.04-1.20), lifting (OR 1.08, 95% CI 1.02-1.14) and the combination of bending and lifting (OR 1.14, 95% CI 1.01-1.29). Conclusions Moderate to high-quality evidence is available that LRS can be classified as a work-related disease depending on the level of exposure to bending of the trunk or lifting and carrying. Professional driving and sitting were not significantly associated with LRS.