Background Psychosocial problems such as depression, anxiety, and substance abuse are common and burdensome in young people. In New Zealand, screening for such problems is undertaken routinely only with year 9 students in low-decile schools and opportunistically in pediatric settings using a nonvalidated and time-consuming clinician-administered Home, Education, Eating, Activities, Drugs and Alcohol, Sexuality, Suicide and Depression, Safety (HEEADSSS) interview. The Youth version, Case-finding and Help Assessment Tool (YouthCHAT) is a relatively new, locally developed, electronic tablet–based composite screener for identifying similar psychosocial issues to HEEADSSS Objective This study aimed to compare the performance and acceptability of YouthCHAT with face-to-face HEEADSSS assessment among 13-year-old high school students. Methods A counterbalanced randomized trial of YouthCHAT screening either before or after face-to-face HEEADSSS assessment was undertaken with 129 13-year-old New Zealand high school students of predominantly Māori and Pacific Island ethnicity. Main outcome measures were comparability of YouthCHAT and HEEADSSS completion times, detection rates, and acceptability to students and school nurses. Results YouthCHAT screening was more than twice as fast as HEEADSSS assessment (mean 8.57 min vs mean 17.22 min; mean difference 8 min 25 seconds [range 6 min 20 seconds to 11 min 10 seconds]; P<.01) and detected more issues overall on comparable domains. For substance misuse and problems at home, both instruments were roughly comparable. YouthCHAT detected significantly more problems with eating or body image perception (70/110, 63.6% vs 25/110, 22.7%; P<.01), sexual health (24/110, 21.8% vs 10/110, 9.1%; P=.01), safety (65/110, 59.1% vs 17/110, 15.5%; P<.01), and physical inactivity (43/110, 39.1% vs 21/110, 19.1%; P<.01). HEEADSSS had a greater rate of detection for a broader set of mental health issues (30/110, 27%) than YouthCHAT (11/110, 10%; P=.001), which only assessed clinically relevant anxiety and depression. Assessment order made no significant difference to the duration of assessment or to the rates of YouthCHAT-detected positive screens for anxiety and depression. There were no significant differences in student acceptability survey results between the two assessments. Nurses identified that students found YouthCHAT easy to answer and that it helped students answer face-to-face questions, especially those of a sensitive nature. Difficulties encountered with YouthCHAT included occasional Wi-Fi connectivity and student literacy issues. Conclusions This study provides preliminary evidence regarding the shorter administration time, detection rates, and acceptability of YouthCHAT as a school-based psychosocial screener for young people. Although further research is needed to confirm its effectiveness in other age and ethnic groups, YouthCHAT shows promise for aiding earlier identification and treatment of common psychosocial problems in young people, including possible use as part of an annual, school-based, holistic health check. Trial Registration Australian New Zealand Clinical Trials Network Registry (ACTRN) ACTRN12616001243404p; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371422.