Background Increasing physical activity among girls is a public health priority. Peers play a central role in influencing adolescent behaviour. Peer-led interventions may increase physical activity in adolescent girls, and a feasibility trial had shown that PLAN-A (Peer-led physical Activity iNtervention for Adolescent girls) had evidence of promise to increase physical activity in adolescent girls. Objective The objective was to test whether or not PLAN-A can increase adolescent girls’ physical activity, relative to usual practice, and be cost-effective. Design This was a two-arm, cluster-randomised controlled trial, including an economic evaluation and a process evaluation. Participants State-funded secondary schools in the UK with girls in Year 9 (aged 13–14 years) participated in the trial. All Year 9 girls in participating schools were eligible. Randomisation Schools were the unit of allocation. They were randomised by an independent statistician, who was blinded to school identities, to the control or intervention arm, stratified by region and the England Index of Multiple Deprivation score. Intervention The intervention comprised peer nomination (i.e. identification of influential girls), train the trainers (i.e. training the instructors who delivered the intervention), peer supporter training (i.e. training the peer-nominated girls in techniques and strategies underpinned by motivational theory to support peer physical activity increases) and a 10-week diffusion period. Outcomes The primary outcome was accelerometer-assessed mean weekday minutes of moderate to vigorous physical activity among Year 9 girls. The follow-up measures were conducted 5–6 months after the 10-week intervention, when the girls were in Year 10 (which was also 12 months after the baseline measures). Analysis used a multivariable, mixed-effects, linear regression model on an intention-to-treat basis. Secondary outcomes included weekend moderate to vigorous physical activity, and weekday and weekend sedentary time. Intervention delivery costs were calculated for the economic evaluation. Results A total of 33 schools were approached; 20 schools and 1558 pupils consented. Pupils in the intervention arm had higher Index of Multiple Deprivation scores than pupils in the control arm. The numbers randomised were as follows: 10 schools (n = 758 pupils) were randomised to the intervention arm and 10 schools (n = 800 pupils) were randomised to the control arm. For analysis, a total of 1219 pupils provided valid weekday accelerometer data at both time points (intervention, n = 602; control, n = 617). The mean weekday moderate to vigorous physical activity was similar between groups at follow-up. The central estimate of time spent engaging in moderate to vigorous physical activity was 2.84 minutes lower in the intervention arm than in the control arm, after adjustment for baseline mean weekday moderate to vigorous physical activity, the number of valid days of data and the stratification variables; however, this difference was not statistically significant (95% confidence interval –5.94 to 0.25; p = 0.071). There were no between-arm differences in the secondary outcomes. The intervention costs ranged from £20.85 to £48.86 per pupil, with an average cost of £31.16. Harms None. Limitations The trial was limited to south-west England. Conclusions There was no evidence that PLAN-A increased physical activity in Year 9 girls compared with usual practice and, consequently, it was not cost-effective. Future work Future work should evaluate the utility of whole-school approaches to promote physical activity in schools. Trial registration This trial is registered as ISRCTN14539759. Funding This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 6. See the NIHR Journals Library website for further project information. This trial was designed and delivered in collaboration with the Bristol Randomised Trials Collaboration (BRTC), a United Kingdom Clinical Research Commission (UKCRC)-registered Clinical Trials Unit that, as part of the Bristol Trials Centre, is in receipt of NIHR Clinical Trials Unit support funding. The sponsor of this trial was University of Bristol, Research and Enterprise Development www.bristol.ac.uk/red/. The costs of delivering the intervention were funded by Sport England.