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High-energy ionizing radiation therapy is a highly effective method for destroying cancer cells. Monitoring the dose distribution during radiation therapy is extremely important to deliver an optimal X-ray dose to diseased areas and minimize radiation exposure to adjacent healthy tissues. Here, we present an X-ray acoustic (XA) dosimetry system that successfully combines a spherically focused ultrasound (US) transducer with a medical linear accelerator. The system can be potentially utilized in clinical radiation therapy as an intratherapy dosimetry tool. The measured XA signal showed good correlation with the water-absorbed dose measured with conventional dosimetry. We acquired the absorbed X-ray dose distribution in a lead sample by mechanically scanning the focused US transducer. The lateral spatial resolution of the XA signal was 2.1 ± 0.5 mm, and signal-to-noise ratio of the signal was maintained with …