OBJECTIVES: Systemic sclerosis (SSc) patients have psychological distress and poor well-being and need a tailored treatment. Psychological interventions, rarely tested for efficacy, showed poor benefits. The present randomized controlled trial tested the efficacy of Well-Being Therapy (WBT) in SSc patients. METHODS: Thirty-two outpatients were randomized (1:1) to WBT (n = 16) or Treatment As Usual (i.e. routine medical check-ups) (TAU) (n = 16). Primary outcome was well-being. Secondary outcomes included functional ability related to SSc, psychological distress, mental pain, suffering. All participants were assessed at baseline (T0). The WBT group was assessed after two months (end of WBT session 4) (T1), after four months (end of WBT session 8) (T2), after seven months (3-month follow-up) (T3) and after 10 months (6-month follow-up) (T4). The TAU group was assessed two (T1), four (T2), seven (T3) and ten (T4) months after baseline. RESULTS: WBT produced a significant improvement in subjective well-being (P ≤ 0.001), personal growth (P = 0.006), self-acceptance (P = 0.003) compared with TAU, maintained at T3 as what concerns subjective well-being (P = 0.012). WBT produced a greater decrease in psychological distress (P = 0.010), mental pain (P = 0.010), suffering (P ≤ 0.001) compared with TAU, maintained at T4 as what concerns suffering (P ≤ 0.001). Participants reported high satisfaction with WBT. CONCLUSION: The study provides preliminary evidence on the benefits of WBT as short-term approach for in- and out-patient SSc healthcare paths. Studies with larger samples are needed to have the evidence for recommending WBT to SSc patients.