We studied the effects of antimicrobial prophylaxis and possible predictors of failure in multiple sclerosis patients with bacteriuria and bladder dysfunction. patients were categorized into 3 groups, according to post-voided residual urine volume (PVR): patients with indications for self-intermittent catheterization (SIC) who elected (Group A, n=39) or not (Group B, n=53) to use SIC and patients with no indication for SIC (Group C, n=75). In group A, 90% of patients developed bacteriuria after SIC. Rates of bacteriuria in groups B and C were significantly lower (34% and 24%, respectively, all p<0.001). Prophylaxis failed in 31% and 22% of patients in groups A and b, respectively whereas all group C patients responded to prophylaxis. Symptomatic urinary tract infection was observed only in 14% of group A patients. Significant predictors of prophylaxis failure were an expanded disability status scale (EDSS) score >6 (p<0.05), a high pVR (p<0.075) and resistance to prophylaxis regimen (p<0.007). SIC did not have a significant association with prophylaxis failure. In multivariate analysis only a higher eDSS score (>6) predicted prophylaxis failure (p=0.019).