There is limited research to investigate the relationship between blood urea nitrogen (BUN) levels and gout, especially there was no study to establish a causal relationship. The aim of our study is to explore the associations between BUN levels and gout risk using observational and Mendelian randomization (MR) analyses. In the observational analyses, we used data from the 2007 to 2018 survey cycles of the National Health and Nutrition Examination Survey (NHANES) and recruited 31,245 participants aged ≥ 20 years. Logistic regression, subgroup analyses, restricted cubic spline (RCS), and the 2-sample MR analysis were used to examine the association between BUN levels with gout. Our cross-sectional study found that each standard deviation increase in BUN was linked to an elevated risk of gout after adjusting for covariates (odds ratio [OR] = 1.02, 95% confidence intervals [CI] = 1.01-1.03, P < .001). In subgroup analyses, stronger associations between BUN and gout were identified in female, hypertension, diabetes, and chronic kidney disease (CKD) (all P < .05). In addition, the RCS revealed positive non-linear relationship between BUN and gout. The 2-sample MR analyses results suggested that there were positive causal relationships between BUN and gout using the Inverse variance weighted (IVW) method (OR = 9.12, 95% CI = 2.00-41.52], P = .0042), (OR = 5.98, 95% CI = 2.15-16.62, P = .0006]), and (OR = 1.43, 95% CI = 1.02-1.92], P = .0367). Our study found the robust and causal relationship between BUN levels and the risk of gout. These results suggest that BUN can be used as a feasible indicator for predicting gout.