Objective: To investigate the efficacy of a treatment with low‐dose intravenous cyclophosphamide (CYC) and low‐dose prednisone in early diffuse cutaneous systemic sclerosis (dcSSc). Methods: Patients with dcSSc and a disease duration <24 months consecutively admitted to a tertiary centre underwent a prospective 1‐year study. They were treated with i.v. CYC 500 mg/pulses, 10 mg prednisone equivalent, and supportive therapy. Modified Rodnan skin score (mRss), Health Assessment Questionnaire – Disability Index (HAQ‐DI), forced vital capacity (FVC), and diffusing lung capacity for CO (DLCO) were assessed as outcome measures. In addition, the nine Medsger severity scale scores were evaluated. Results: mRss and DLCO significantly improved at both 6 (p = 0.002 and 0.012, respectively) and 12 months (p = 0.002 and 0.003, respectively). HAQ‐DI showed a nearly significant reduction at 12 months (p = 0.06). Medsger's severity scores also improved for general condition (p = 0.001), peripheral vascular (p = 0.05), skin (p = 0.02), joint/tendon (p = 0.001), muscle (p = 0.05), and lung (p = 0.02). No treatment interruption was needed. Conclusions: This preliminary study suggests a role for low‐dose i.v. CYC in the treatment of early dcSSc. Controlled studies are warranted.