Introduction. Hematopoietic stem cell transplantation is an effective therapy in many hematological diseases. Purpose. The objective of the study was to compare the influence of antimicrobial prophylaxis with unabsorbable rifaximin and systemic ciprofloxacin on infectious complications in hematopoietic stem cell transplant patients. Materials and methods. As antibiotic prophylaxis, ciprofloxacin was given to 40 patients, and rifaximin – to 31. Frequency of fever episodes, bacteremia, sepsis, pneumonia, fungemia, number of antibiotics used and duration of their use, frequency of bacterial resistance to ciprofloxacin and presence of multidrug resistant bacteria were compared. Results. Significant reduction of duration of antibiotic treatment was observed in the ciprofloxacin group (7vs 10 days). With bacteremia, the rate of resistance to ciprofloxacin was 30% in the rifaximin group and 100% in the ciprofloxacin group. Multidrug resistant bacteria were reported more often in the ciprofloxacin group. The other parameters of infectious complications were comparable in both groups. Conclusions. The efficacy of rifaximin and ciprofloxacin in prophylaxis of infectious complications seems to be comparable in the study group. High resistance to ciprofloxacin in the study group could reduce preventive effect of prophylactic ciprofloxacin.