As a well-established single-modality approach for early-stage prostate cancer, transperineal interstitial permanent prostate brachytherapy (TIPPB) has gained increasing popularity due to its favorable clinical results. Currently, three isotopes, namely Cs-131, I-125, and Pd-103, are commercially available for TIPPB. This is the first study to systematically explore the dosimetric difference of these three isotopes for TIPPB. In total, 25 patients with T1-T2c prostate cancer previously implanted with I-125 seeds were randomly selected and replanned with Cs-131, I-125, and Pd-103 seeds to the prescription doses of 115, 145, and 125 Gy, respectively. The planning goals attempted were prostate V(p)100 approximately 95%, D(p)90 >or= 100%, and prostatic urethra D(u)10 <or= 150%. The dosimetric parameters, as well as the number of seeds and needles required, were analyzed and compared. The mean homogeneity index (HI) was 0.59, 0.56, and 0.46 for Cs-131, I-125, and Pd-103 plans, respectively. The average D(u)10 was 124.6%, 125.7%, and 129.7%, respectively. The average rectum V(r)100 was 0.19, 0.22, and 0.31 cc, respectively. In addition, the average number of seeds was 57.9, 63.0, and 63.7, and the average number of needles required was 31.6, 32.9, and 33.6 for Cs-131, I-125, and Pd-103 seeds, respectively. This study demonstrates that TIPPB, utilizing Cs-131 seeds, allows for better dose homogeneity, while providing comparable prostate coverage and sparing of the urethra and rectum, with a comparable number of, or fewer, seeds and needles required, compared to I-125 or Pd-103 seeds. Further biological and clinical studies associated with Cs-131 are warranted.