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The aim of this study was to determine the efficacy, safety and acceptability of a 4-week very-low-energy diet (VLED) program for adolescents with obesity. Adolescents (13–17 years) with obesity and ≥1 obesity-related complication were Fast Track to Health 52-week randomized controlled trial participants. Adolescents undertook a 4-week micronutrient-complete VLED (800 kcal/day), with weekly dietitian support. Anthropometric data were recorded at baseline and week-4 and side-effects at day 3–4, week-1, -2, -3 and -4. Adolescents completed an acceptability survey at week-4. A total of 134 adolescents (14.9 ± 1.2 years, 50% male) had a 5.5 ± 2.9 kg (p < 0.001) mean weight loss at week-4: 95% experienced ≥1 and 70% experienced ≥3 side-effects during the VLED program, especially during the first week. Hunger, fatigue, headache, irritability, loose stools, constipation and nausea were most common. Reporting more side-effects at day 3–4 correlated with greater weight loss at week-4 (r = −0.188, p = 0.03). Adolescents reported 'losing weight' (34%) and 'prescriptive structure' (28%) as the most positive aspects of VLED, while 'restrictive nature' (45%) and 'meal replacement taste' (20%) were least liked. A dietitian-monitored short-term VLED can be implemented safely and is acceptable for many adolescents seeking weight loss, despite frequent side-effects. Investigating predictors of acceptability and effectiveness could determine adolescents most suited to VLED programs. [ABSTRACT FROM AUTHOR]