Introduction: The aim of the present study is to compare a hydrophilic catheter to the standard polyvinyl chloride catheter with regard to bacteriological safety and overall comfort in patients undergoing intravesical immuno- or chemotherapy for bladder cancer. Materials and Methods: One hundred patients (80 males, 20 females; median age 65.8 years, range 48–79 years) eligible for intravesical prophylaxis of superficial bladder cancer recurrences were randomized to receive intravesical therapy using a standard catheter (group A, n = 50) or a hydrophilic catheter (group B, n = 50). Urinalysis and urine culture were performed 2 days after catheterization. Comfort during catheterization was assessed by a 5-point visual analogue scale at the end of the first four instillations. Results: Urinary tract infection (UTI) was detected in 7.4% of catheterizations in group A, whereas it occurred in 3.5% of catheterizations in group B (p < 0.01). Escherichia coli was the most frequent pathogen regardless of the device used. At the end of each of the first four instillations, the mean score for discomfort was significantly higher in group A than in group B (p < 0.001), although catheterization was progressively better tolerated regardless of the device used (both p < 0.005). None of the patients were found to be suffering from orchitis, epididymitis or gross haematuria. Conclusion: Hydrophilic catheters may be used safely and are well tolerated by patients undergoing intravesical immuno- or chemotherapy. The hydrophilic catheter was associated with a significantly lower occurrence of UTI and higher acceptability compared to the standard device. These data should be considered with regard to patient compliance with intravesical therapy.