Polymyalgia rheumatica (PMR) has a marked preponderance in women. The female sex has been claimed to be a risk factor for longer-course corticosteroid therapy and to be associated with more severe systemic symptoms and lower hemoglobin levels. Eighty consecutive patients affected by PMR, seen at two tertiary referral centers, were followed-up for a mean period of 14.9 months after initiating corticosteroid treatment. At presentation, women had longer disease duration and lower hemoglobin levels (both P = 0.05) than men. In contrast, their systemic signs of PMR were less common (P = 0.01). Women were treated with a slightly higher mean daily dose of prednisone (P = 0.055), and assumed a significantly higher cumulative dosage of the drug (P = 0.01). Accordingly, the mean number of steroid-related side effects was higher among women (P = 0.003). The number of relapses during steroid treatment (P = 0.02), but not that of recurrences, was increased in women. ESR, which was raised at presentation, significantly declined during follow-up to normal values in both subgroups (P < 0.00001 by analysis of variance [ANOVA]). Its decrease was significantly more pronounced in men than in women. Hemoglobin at follow-up was significantly higher in men than in women at any given time point. In conclusion, sex is probably modulating the response to corticosteroids. This finding emphasizes the need to consider differences between males and females in the clinical and therapeutic approach to PMR patients.