ABSTRACT Purpose One of the greatest concerns among clinicians regarding testosterone replacement therapy (TRT) is the fear of causing or promoting prostate cancer. We evaluated prostatic changes in hypogonadal men with and without high grade prostatic intraepithelial neoplasia (PIN), which is considered a prostatic precancerous lesion, after 1 year of TRT. Materials and Methods A total of 75 hypogonadal who completed 12 months of TRT were studied. All underwent prostate biopsy prior to initiating treatment. Of the men 55 had benign prostate biopsies (PIN−) and 20 had PIN without frank cancer (PIN+). All men with PIN underwent repeat biopsy to exclude cancer prior to the initiation of testosterone treatment. Prostate specific antigen (PSA), and total and free testosterone were determined prior to treatment and at 1 year. Repeat biopsy was performed for a change noted on digital rectal examination or for a PSA increase of 1 ng/l or greater. Results PSA was similar at baseline in men with and without PIN (1.49 ± 1.1 and 1.53 ± 1.6 ng/dl, p >0.05) and after 12 months of TRT (1.82 ± 1.1 and 1.78 ± 1.6 ng/dl, respectively, p >0.05). A slight, similar increase in mean PSA was noted in the PIN− and PIN+ groups (0.25 ± 0.6 and 0.33 ± 0.6 ng/dl, p >0.05). One man in the PIN+ group had cancer after biopsy was performed due to abnormal digital rectal examination. Four additional men in the PIN− group and 2 in the PIN+ group underwent re-biopsy for elevated PSA and none had cancer. No differences were noted between the PIN− and PIN+ groups with regard to total and free testosterone at baseline and at 1 year (p = 0.267). Conclusions After 1 year of TRT men with PIN do not have a greater increase in PSA or a significantly increased risk of cancer than men without PIN. These results indicate that TRT is not contraindicated in men with a history of PIN.