ABSTRACT Purpose: To our knowledge we report the first long-term use of desmopressin for nocturia. Patients previously responding to desmopressin in short-term studies were enrolled in this long-term open label study. Materials and Methods: Patients received treatment for 10 or 12 months with the optimal desmopressin dose (0.1, 0.2 or 0.4 mg orally at bedtime). Patients were followed a further month without treatment. Of the patients completing the short-term study 132 males (92%) and 117 females (83%) were recruited, and 95 (72%) and 87 (75%), respectively, completed long-term treatment. Results: The mean number of nocturnal voids was decreased in males and females throughout the study (1.3 to 1.6 and 1.2 to 1.3) compared with baseline (3.1 and 2.9, respectively). After followup the number of voids increased after treatment cessation. From baseline to 12 months the mean duration of the first sleep period gradually increased in males (157 to 288 minutes) and females (142 to 310 minutes). After followup the mean duration of the first sleep period decreased, confirming that it was a treatment related benefit. Desmopressin was well tolerated with few males (14%) or females (10%) withdrawing due to adverse events. Most adverse events were mild (44%) or moderate (44%) in severity. Four males experienced serious drug related adverse events, namely dizziness in 1, cardiac failure, headache and vomiting in 2, and chest pain and hypertension in 1. A female experienced 4 serious drug related adverse events, that is hyponatremia, headache, nausea and vertigo. Two patients had clinically significant hyponatremia. Conclusions: This long-term study shows that desmopressin is a generally well tolerated and effective treatment for nocturia.