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Objective: Despite promising results for compassion-focused therapy (CFT) as self-help, larger-scale trials including long-term follow-up data are needed to establish its effectiveness in the context of public mental health. Empirical evidence supporting its effectiveness in improving well-being is lacking. In a randomized controlled trial, the effects of CFT as guided self-help on well-being were evaluated. Method: Adults (mean age = 52.87, SD = 9.99, 74.8% female) with low to moderate levels of well-being were recruited in the Dutch population and randomized to CFT (n = 120) or a waitlist control group (n = 122). Participants completed the Mental Health Continuum–Short Form (well-being), Hospital Anxiety and Depression Scale (depression and anxiety), Perceived Stress Scale (stress), Self-Compassion Scale–Short Form (self-compassion), Forms of Self-Criticizing/Attacking and Reassurance Scale (self-criticism and self-reassurance), Positive and Negative Affect Schedule (positive/negative affect), and Gratitude questionnaire (gratitude) at baseline, postintervention (3 months), 3- and 9-month follow-up. Results: Compared with the waitlist control group, the CFT group showed superior improvement on well-being at postintervention, d = .51, 95% CI [.25, .77], p < .001, and 3-month follow-up, d = .39, 95% CI [.13, .65], p < .001. No significant moderators were found. On all secondary outcome measures but positive affect, the intervention group showed significantly greater improvements up to 3-month follow-up. At 9-month follow-up, improvements on all measures were retained or amplified among CFT participants. Conclusions: CFT as guided self-help shows promise as a public mental health strategy for enhancing well-being and reducing psychological distress.