Background and Purpose: During the past decade, the incidence of severe infections after transrectal ultrasonography-guided prostate biopsy has increased. Antibacterial sustained-release varnish has been shown to reduce bacterial infections. This varnish has yet to be tested in the field of urology. We undertook an in vitro study to assess the possibility of reducing infection rates after prostate biopsy by coating the needle with a novel sustained, yet rapid release chlorhexidine varnish (SRV-CHX) specifically modified for prostate biopsy. Materials and Methods: A model simulating the microbiologic environment of a prostate biopsy was developed. The model consisted of two layers of agar, of which the first represented the rectum and was preinfected with Escherichia coli. The second layer was sterile and represented tissue interposed between the rectum and prostate. SRV-CHX-coated biopsy needles were inserted 12 times through the two layers, into the third agar layer representing the prostate. Infection transmission was determined by assessing bacterial growth at inoculation sites within the agar plate representing the prostate. Bacterial growth inhibition was measured as an inhibition zone on the contaminated agar. Results: Testing the antibacterial effect of the SRV-CHX-coated needle, we found a substantial reduction of infection transmission as well as sustained inhibition of bacterial growth compared with control needles. Conclusions: Needles coated with SRV-CHX offer a new strategy in infection control after prostate biopsy. A new strategy of SRV-coated prostate biopsy needles supplemented with various antibacterial agents, combined with prophylactic oral antibiotics should result in decreased infection rates after prostate biopsies. Further in vitro studies are needed to formulate the SRV with an optimal antibacterial agent.