To evaluate exclusion of prostate cancer (PCa) by using empiric antibiotic treatment for patients with total prostate specific antigen (PSA) between 4-10 ng/ml. A hundred asymptomatic men with a PSA between 4-10 ng/ml and normal digital rectal examination (DRE) were enrolled in this randomized prospective study. The treatment group (n=50) was given 400 mg of ofloxacin daily for 4 weeks, whereas the control group (n=50) was followed without any treatment. At the end of the four weeks, repeat PSA were measured and all patients underwent transrectal ultrasound (TRUS) guided biopsy, regardless of the repeat PSA levels. Totally 22 patients (22%) had prostate cancer (9 in treatment group and 13 in control group). A significant PSA decrease was observed in the treatment group at repeat PSA measurements (p=0.001). The PSA drop was also significantly more in patients without PCa than with PCa (p=0.028). In patients whose repeat PSA after antibiotic treatment decreased below 4 ng/ml, 2 times as many patients (16.6%) had PCa in the control group when compared with the treatment group (8.3%). On the other hand, in patients whose repeat PSA remained above 4 ng/ml, PCa was detected in 27.3% of the patients in the control group and 21% in the treatment group. Empirical antibiotic treatment in asymptomatic patients with a PSA level 4-10 ng/ml and a normal DRE may be used to select prostate biopsy candidates. Studies with higher number of patients may result in more powerful associations with narrower confidence intervals for increased confidence.