Spinal cord-injured (SCI) patients often suffer from symptomatic polymicrobial urinary tract infection (UTI). The objective of this study was to evaluate the clinical outcome and cost-savings associated with antibiotic therapy based on limited vs full microbiological investigation of urine cultures in adult SCI patients with symptomatic polymicrobial UTI (> or = 2 organisms growing in urine cultures). In the first part of the study, a total of 40 evaluable patients were prospectively randomized in a single-blinded fashion to receive antibiotic therapy based on either limited (21 patients) or full microbiologic investigation (19 patients) of urine cultures. The practicality of a limited microbiological investigation was further examined in the second part of the study where 12 consecutive patients with symptomatic polymicrobial UTI initially had only limited microbiological investigation of urine cultures and received antibiotic therapy accordingly. When analyzing all patients in the study, the likelihood of adequate clinical response was not significantly different between those who received antibiotic therapy based on limited (28/33 = 85%) vs full (18/19 = 95%) microbiological investigation of urine cultures (P = 0.40). An average of 183 US dollars could be saved per patient by managing symptomatic polymicrobial UTI based on a limited vs a full microbiological investigation. These results suggest that in adult SCI patients with symptomatic polymicrobial UTI antibiotic therapy guided by a limited microbiological investigation may be practical, adequate and cost-saving.