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To investigate the effectiveness of a school‐based multiple health behaviour change e‐health intervention for modifying risk factors for chronic disease (secondary outcomes). Cluster randomised controlled trial. Students (at baseline [2019]: year 7, 11–14 years old) at 71 Australian public, independent, and Catholic schools. Health4Life: an e‐health school‐based multiple health behaviour change intervention for reducing increases in the six major behavioural risk factors for chronic disease: physical inactivity, poor diet, excessive recreational screen time, poor sleep, and use of alcohol and tobacco. It comprises six online video modules during health education class and a smartphone app. Comparison of Health4Life and usual health education with respect to their impact on changes in twelve secondary outcomes related to the six behavioural risk factors, assessed in surveys at baseline, immediately after the intervention, and 12 and 24 months after the intervention: binge drinking, discretionary food consumption risk, inadequate fruit and vegetable intake, difficulty falling asleep, and light physical activity frequency (categorical); tobacco smoking frequency, alcohol drinking frequency, alcohol‐related harm, daytime sleepiness, and time spent watching television and using electronic devices (continuous). A total of 6640 year 7 students completed the baseline survey (Health4Life: 3610; control: 3030); 6454 (97.2%) completed at least one follow‐up survey, 5698 (85.8%) two or more follow‐up surveys. Health4Life was not statistically more effective than usual school health education for influencing changes in any of the twelve outcomes over 24 months; for example: fruit intake inadequate: odds ratio [OR], 1.08 (95% confidence interval [CI], 0.57–2.05); vegetable intake inadequate: OR, 0.97 (95% CI, 0.64–1.47); increased light physical activity: OR, 1.00 (95% CI, 0.72–1.38); tobacco use frequency: relative difference, 0.03 (95% CI, –0.58 to 0.64) days per 30 days; alcohol use frequency: relative difference, –0.34 (95% CI, –1.16 to 0.49) days per 30 days; device use time: relative difference, –0.07 (95% CI, –0.29 to 0.16) hours per day. Health4Life was not more effective than usual school year 7 health education for modifying adolescent risk factors for chronic disease. Future e‐health multiple health behaviour change intervention research should examine the timing and length of the intervention, as well as increasing the number of engagement strategies (eg, goal setting) during the intervention. Australian New Zealand Clinical Trials Registry: ACTRN12619000431123 (prospective).