Background Patients with spinal cord injury (SCI) who carry indwelling urinary catheters have an increased risk of urinary tract infection (UTI). Antiseptic silver alloy-coated (SAC) silicone urinary catheters prove to be a promising intervention to reduce UTIs; however, current evidence cannot be extrapolated to patients with SCI. Purpose This study aimed to assess the efficacy of SAC urinary catheters for preventing catheter-associated urinary tract infections. Design/Setting This is an open-label, multicenter (developed in Spain, Portugal, Chile, Turkey, and Italy), randomized clinical trial conducted in 14 hospitals from November 2012 to December 2015. Patient Sample Eligible patients were men or women with traumatic or medical SCI, aged ≥18 years, requiring an indwelling urinary catheter for at least 7 days. Outcome Measures The primary outcome was the incidence of symptomatic UTIs. The secondary outcome included bacteremia in the urinary tract and adverse events. Materials and Methods Patients were randomized to receive a SAC urinary catheter (experimental group) or a standard catheter (control group) for at least 7 days. Data were compared using chi-squared test and also calculating the absolute risk difference with a 95% confidence interval. An adjusted analysis including different risk factors of UTI was performed. This study was mainly funded by La Marató de TV3 Foundation (grant number # 112210) and the European Clinical Research Infrastructures Network organization. The funders had no role in the interpretation or reporting of results. Results A total of 489 patients were included in the study, aged 55 years in the experimental group and aged 57 in the control group (p=.870); 72% were men; 43% were hospitalized patients, and 57% were outpatients (p=1.0). The most frequent cause of SCI was traumatic (73.75%), and the localization was mainly the cervical spine (42.74%). Most of the patients had an A score (complete spinal injury and no motor and sensory is preserved) on the ASIA scale (62.37%). The median time of urethral catheterization was 27 days in the experimental group and 28 days in the control group (p=.202). Eighteen patients (7.41%) in the experimental group and 19 in the control (7.72%) group had a symptomatic UTI (odds ratio [OR] 0.96 [0.49–1.87]). The adjusted analysis revealed no change in the results. Only three patients in the experimental group had bacteremia within the urinary tract. The experimental group presented more adverse events related to the use of a catheter than the control group (OR 0.03 [0.00–0.06]). Conclusions The results of this study do not support the routine use of indwelling antiseptic SAC silicone urinary catheters in patients with SCI. However, UTIs associated to long-term urinary catheter use remain a challenge and further investigations are still needed.