PURPOSE: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings.METHODS AND MATERIALS: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P+), the biologically effective uniform dose, and the generalized equivalent uniform dose index.RESULTS: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1×20 Gy, 98.6% in 2×14 Gy, 97.5% in 3×11 Gy, and 97.8% in 4×9.5 Gy. The corresponding P+ values were 88.8% in 1×20 Gy, 83.9% in 2×14 Gy, 86.0% in 3×11 Gy, and 82.3% in 4×9.5 Gy. With use of the fractionation scheme 4×9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1×19.68 Gy, 2×13.75 Gy, and 3×11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1×19.16 Gy with a P+ of 91.8%, 2×13.2 Gy with a P+ of 89.6%, 3×10.6 Gy with a P+ of 88.4%, and 4×9.02 Gy with a P+ of 86.9%.CONCLUSIONS: Among the fractionation schemes 1×20 Gy, 2×14 Gy, 3×11 Gy, and 4×9.5 Gy, the first scheme was more effective in terms of P+. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4×9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%.