IntroductionChildhood cancer survivors (CCS) are at risk of experiencing lower quality‐of‐life, fatigue, and depression. Few randomized controlled trials have studied the effect of physical activity (PA) on these in adult long‐term CCS. This study investigated the effect of a 1‐year individualized PA intervention on health‐related quality‐of‐life (HRQOL), fatigue, and distress symptoms in adult CCS.MethodsThe SURfit trial randomized 151 CCS ≥16 years old, <16 at diagnosis and ≥5 years since diagnosis, identified through the Swiss Childhood Cancer Registry. Intervention participants received personalized PA counselling to increase intense PA by ≥2.5 h/week for 1 year. Controls maintained usual PA levels. The authors assessed physical‐ and mental‐HRQOL, fatigue, and distress symptoms at baseline, 3, 6, and 12 months. T‐scores were calculated using representative normative populations (mean = 50, standard deviation = 10). Generalized linear mixed‐effects models with intention‐to‐treat (ITT, primary), and three per‐protocol allocations were used.ResultsAt 12 months, ITT (–3.56 larger decrease, 95% confidence interval –5.69 to –1.43, p = .001) and two per‐protocol analyses found significantly lower fatigue. Physical‐HRQOL improved significantly in two per‐protocol analyses at 12 months. No other effects were found.ConclusionSURfit showed that increased intense PA over 1 year improved fatigue in adult CCS. Survivors should be recommended PA to reduce the burden of late‐effects.