Introduction The built environment defines opportunities for healthy eating and physical activity and may thus be related to blood lipids. The aim of this study is to systematically analyse the scientific evidence on associations between built-environment characteristics and blood lipid levels in adults. Methods PubMed, EMBASE and Web of Science were searched for peer-reviewed papers on population-based studies up to 9 October 2017. We included studies that reported on built-environment characteristics and blood lipid levels in adult populations (≥18 years). Two reviewers independently screened titles/abstracts and full-Texts of papers and appraised the risk of bias of included studies using an adapted version of the Quality Assessment Tool for Quantitative Studies. We performed meta-Analyses when five or more studies had sufficient homogeneity in determinant and outcome. Results After screening 6902 titles/abstracts and 141 potentially relevant full-Text articles, we included 50 studies. Forty-seven studies explored associations between urban versus rural areas with blood lipid levels. Meta-Analyses on urban versus rural areas included 133 966 subjects from 36 studies in total. Total cholesterol levels were significantly and consistently higher in urban areas as compared with rural areas (mean difference 0.37 mmol/L, 95% CI 0.27 to 0.48). Urban/rural differences in high density lipoprotein cholesterol were inconsistent across studies and the pooled estimate showed no difference (0.00 mmol/L 95% CI '0.03 to 0.04). Low density lipoprotein (LDL) cholesterol and triglyceride levels were higher in urban than in rural areas (mean difference 0.28, 95% CI 0.17 to 0.39 and 0.09, 95% CI 0.03 to 0.14, respectively). Conclusions Total and LDL cholesterol levels and triglycerides were consistently higher in residents of urban areas than those of rural areas. These results indicate that residents of urban areas generally have less favourable lipid profiles as compared with residents of rural areas. Prospero registration number CRD42016043226.