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To assess the efficacy of desmopressin nasal spray compared with diclofenac given intramuscularly in patients with acute renal colic caused by urolithiasis.The study included 61 patients randomized into three different groups; group A received desmopressin (40 µg, nasal spray), group B diclofenac (75 mg) intramuscularly and group C, both desmopressin and diclofenac. Pain was assessed using a visual analogue scale (a 10-cm horizontal scale ranging from ‘no pain’ to ‘unbearable pain’) at baseline, 10, 20 and 30 min after administering the treatments.On admission, the pain level was the same in all three groups. At 10 min the pain decreased in all groups to a level that was not significantly different. At 20 min groups B and C had similar mean pain levels (3.7), whereas in group A it was 5.0. At 30 min, groups B and C scored 2–3, and group A 5.6. All three treatments were equally effective at 10 and 20 min but at 30 min there was a stabilization/slight increase in pain level in group A.Desmopressin has several advantages, e.g. ease of administration, simplicity of delivery and apparent lack of side-effects, which makes it suitable for ambulatory use. Desmopressin acts rapidly and seems to be effective in both single and combined therapy with diclofenac; it decreases the need for a second treatment and increases the analgesic effect of diclofenac. Some patients responded well to desmopressin, with rapid and complete pain relief. These results indicate that desmopressin may be used to treat renal colic either alone or combined, increasing the analgesic effect of other drugs. More studies are needed to validate and confirm the results; it would also be useful to determine factors that may identify the subgroup of patients who respond quickly and with almost complete pain relief.