OBJECTIVE Clinical and technical parameter analysis of patients treated with ultrasound-based image-guided tomotherapeutic IMRT for gallbladder cancer. METHODS Between 8/2001 and 5/2005, 10 patients with primary tumors of the gallbladder were treated by image-guided IMRT to median doses of 59 Gy. To analyze normal tissue radiation exposure reduction using this novel approach, a virtual plan comparison between actually delivered IMRT plans and re-computed plans with identical inverse planning parameters but more conventional PTV safety margins was conducted. RESULTS Average CTV was 379 cm(3), with a mean initial PTV of 834 cm(3). In 9/10 patients, a boost was delivered to a mean CTV(boost) of 171 cm(3) and average PTV(boost) of 241 cm(3). One patient reported RTOG grade 3 acute toxicity. All other patients exhibited Grade 2 or lower acute toxicity. Preliminary median overall survival was 16.7 months (range 3.2-34.9 months), with 5/10 patients alive at analysis. Virtual plan comparison revealed significant organ-at-risk sparing by the enabled PTV margin reduction. CONCLUSIONS Ultrasound-based image-guided IMRT is a feasible mechanism of delivering conformal radiation doses to tumors of the gallbladder with acceptable toxicity. Early outcome data with this novel radiation planning and delivery technique are encouraging and comparable to previously reported literature.