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Purpose: Cone-beam computed tomography (CBCT) is a new image-guided radiation therapy (IGRT) technique for patient alignment in radiotherapy. The CBCT x-ray volume imaging system from Elekta allows for a variety of alignment methods. The aim of this study is to assess the accuracy of soft-tissue-based automatic alignment as compared with manual alignment using intraprostatic fiducials., Methods and Materials: All patients were treated on an Elekta Synergy S linear accelerator with kilovoltage CBCT. All alignments were performed using the x-ray volume imaging system and associated software. Automatic alignment with gray-value-based registration and manual alignment to fiducial markers were performed. Transitional corrections along each axis as well as 3-dimensional vectors were compared with evaluate the accuracy of gray-value-based registration compared with fiducials., Results: The distribution of the 3-dimensional vectors between gray-value and fiducial registrations demonstrated notable differences. The mean summed vector was 0.75 cm, with a standard deviation (SD) of 0.52 cm and range from 0.04 to 2.06 cm. There was minimal difference along the lateral direction, with a mean ± SD of -0.02 cm ± 0.13 cm. However, there were large discrepancies along the superior-inferior and anterior-posterior direction alignments, with mean ± SD values of -0.55 ± 0.48 cm and -0.31 ± 0.43 cm, respectively., Conclusions: CBCT with soft-tissue-based automatic corrections is not an accurate alignment compared with manual alignment to fiducial markers for prostate IGRT. We have concluded that a daily manual alignment to fiducials is one of the most reliable methods to maintain accuracy in prostate IGRT.