Background/Aim: Most patients with multiple brain metastases from melanoma receive whole-brain irradiation. In a previous study, doses >30 Gy resulted in better outcomes than 10x3 Gy. However, the optimal dose-fractionation regimen has not yet been defined. This study compared 20x2 Gy over four weeks, which was used in the previous study, to 12x3 Gy over two-and-a-half weeks. Patients and Methods: Eleven patients treated with 20x2 Gy for multiple brain metastases were compared to 12 patients treated with 12x3 Gy. Results: Intracerebral control rates at 6 and 12 months were 17% and 0% after 20x2 Gy vs. 42% and 11% after 12x3 Gy (p=0.28). Survival rates at 6 and 12 months were 36% and 9% after 20x2 Gy vs. 50% and 25% after 12x3 Gy (p=0.75). Conclusion: The less time-consuming regimen 12x3 Gy appeared not inferior to 20x2 Gy and a reasonable treatment option, particularly for patients with a limited life expectancy.