The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We run a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 ml/minute; 275 patients) and mild (between 60-89 ml/minute; 444 patients). In 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06, 95% CI 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR 0 .67, 95% CI 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR 0.27, 95% CI 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR 2.84, 95% CI 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin.