After transurethral resection (TUR) of superficial bladder tumors, intravesical instillations with BCG are successfully used to lower the recurrence rate. The mechanism of the antitumor activity of BCG is not completely understood. After TUR, a fibrin clot is formed on the damaged urothelium. Fibronectin (FN) is part of the clot. It has been demonstrated that binding of BCG to the bladder wall is mediated by FN, and therefore FN seems necessary for the antitumor activity of BCG. This binding can be inhibited by fibrin clot inhibitors, like aspirin and coumarin. A reduced efficacy of BCG in patients with superficial bladder cancer using these drugs has been described. We studied 183 patients with superficial bladder cancer, treated with one or two 6-week courses of intravesical BCG instillations. Of the 42 patients that used fibrin clot inhibitors, 13 (31%) experienced a recurrent tumor, as compared to 56 (40%) of 141 patients who did not use these drugs (p = 0.28). The mean time to recurrence was the same in both groups. These results did not depend on the BCG strain used (Tice or RIVM, p = 0.92) and were not influenced by the use of antibiotics against urinary tract infections. We conclude that in our study fibrin clot inhibitors have no adverse effect on the efficacy of BCG therapy for superficial bladder cancer.