Aim: To assess the association of genetic variants of catecholamine-O-methyltransferase (COMT) genotypes with acute kidney injury (AKI) and tubular stress after open heart surgery. Patients & methods: We genotyped 195 patients for the COMT-Val158Met polymorphism and measured creatinine, neutrophil gelatinase-associated lipocalin and midkine. We analyzed the association between such polymorphisms and these kidney-related variables. Results: Nonsignificantly more COMT LL patients developed RIFLE-AKI compared with non-LL patients (p = 0.11). Compared with HL and HH patients, LL patients who developed AKI had lower increases in serum creatinine. COMT LL patients had less pronounced release of tubular stress biomarkers (neutrophil gelatinase-associated lipocalin: p = 0.045, midkine: p = 0.072). Conclusion: COMT genotype may associate with different patterns of renal functional changes and tubular stress biomarker release response after open heart surgery.