OBJECTIVE: To compare the efficacy and tolerability of losartan, an antagonist of angiotensin II receptor type 1, with nifedipine for the treatment of primary and secondary Raynaud's phenomenon (RP) in a pilot study. METHODS: In a randomized, parallel-group, controlled trial, patients with primary RP (n = 25) or RP secondary to systemic sclerosis (SSc [scleroderma]; n = 27) were allocated to receive 12 weeks' treatment with either losartan (50 mg/day) or nifedipine (40 mg/day). Primary outcome variables were the severity and frequency of RP episodes and findings on vascular measurements, including thermography and laser Doppler flowmetry. Serum levels of soluble adhesion molecules, endothelin 1, fibrinogen, von Willebrand factor, and procollagen type I N-terminal propeptide (PINP) were also measured. RESULTS: There was a reduction in the severity of RP episodes following treatment with losartan and with nifedipine, but this effect was greater in the losartan arm of the study (P<0.05): episode frequency was reduced only in the losartan group (P<0.01 versus baseline). Symptomatic improvement was associated with a significant reduction in soluble vascular cell adhesion molecule 1 and PINP (P<0.01). Subgroup analysis suggested that although these biochemical changes occurred mainly in SSc patients, the clinical benefit was greater in the primary RP group. CONCLUSION: This study confirms the tolerability of short-term treatment of RP with losartan, and our data suggest its clinical benefit. Further evaluation of this drug as a long-term treatment for SSc-associated RP should be considered, since it may have additional disease-modifying potential.