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Recent findings from an animal experiment suggest a modest association between silymarin and decreased risk of contrast-induced nephropathy. However, the relationship between silymarin and contrast-induced nephropathy in patients with liver cirrhosis remains unclear.From 1997 to 2007, we identified 3019 patients with liver cirrhosis who were administered silymarin and matched them with 3019 patients with liver cirrhosis who were not administered silymarin. Each patient was followed up for a minimum of 4 years. After adjusting for age, gender, hepatitis B, hepatitis C, alcoholic hepatitis, and Charlson comorbidity index, we considered death occurrence and used the Fine and Gray regression models to calculate subdistribution hazard ratios (sHRs) for contrast-induced nephropathy. Sensitivity analyses were also performed using the same model on the subgroups classified by comorbidity.Using the Fine and Gray regression models and with death as the competing risk, we observed that sHR for contrast-induced nephropathy was 0.94-fold higher in the silymarin cohort than in the nonsilymarin cohort (95% confidence interval = 0.61–1.47, P = .791). On the basis of sensitivity analyses results classified by comorbidity, a nonsignificant decrease in risk of contrast-induced nephropathy was found.Silymarin shows no nephron-protective positive effects on contrast-induced nephropathy. Silymarin did not play a nephron-protective role according to Longitudinal Health Insurance Database of Taiwan. Clinical trials are necessary to further assess the nephron-protective effects of silymarin of contrast-induced nephropathy.