<h3>Purpose/Objective(s)</h3> The AVATAR system was the first developed and published radiotherapy (RT) compatible system with radiolucent screen reducing the need for pediatric anesthesia during RT through the use of video-based distraction. Institutional success has been previously demonstrated. This study evaluates the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial. <h3>Materials/Methods</h3> Pediatric patients 3-10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled on study to assess anesthesia use, quality of life (QoL) and anxiety when given the option of AVATAR-based video distraction in lieu of anesthesia. Children able to undergo at least one fraction (fx) of RT using AVATAR without anesthesia were considered successful (S), while those requiring anesthesia for their entire treatment course were non-successful (NS). Institutional success was defined as 50% S patients. QoL and anxiety surveys were administered to each patient and guardian at 3 timepoints: RT simulation, midway through RT, and final treatment. QoL was measured using the PedsQL3.0 Cancer Module survey (PedsQL) administered to both patient and guardian. Anxiety was assessed using the modified Yale Preoperative Assessment Survey Short Form (mYPAS). Success was evaluated using Chi-square test. Survey data from patient/guardian was assessed by type 3 tests of fixed effects. <h3>Results</h3> Sixty-five children were included; median age was 6.7 years. AVATAR was successful at all institutions, and with both photon and proton RT. There were 54 (83%) S patients; anesthesia was avoided for a median of 21 fx per patient. Six S patients required anesthesia at first RT fx but switched to AVATAR within 1-14 fx. Treatment modifications were required for 3, including dosimetric or AVATAR adjustments. Success differed by age (p=0.02) and private versus public insurance (p<0.0001). Success rates did not differ by institution, gender, ethnicity, or need for modifications. For patients who completed all surveys, PedsQL scores did not differ over the RT course, but procedural anxiety significantly decreased (p=0.04). Guardian PedsQL scores for communication significantly improved during treatment (p=0.03). Anxiety decreased for both S and NS patients over RT course (p=0.0002), by age (p=0.03) and by S versus NS patients (p<0.0001). <h3>Conclusion</h3> Across 10 centers, anesthesia avoidance with AVATAR was 83%, compared to age-matched historical controls showing 50% anesthesia avoidance. Procedural and overall anxiety decreased during RT treatment and was lowest among those successful in using AVATAR. AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction. Implementation and data collection regarding the utility of a supportive care intervention among cooperating pediatric RT institutions is achievable in a large multicenter setting.