PURPOSE: To study the safety and efficacy of intranasal desmopressin and intramuscular tramadol versus pethidine for treatment of renal colic. MATERIALS AND METHODS: A total of 90 adult patients who presented with renal colic to the emergency wards were recruited in this study. The patients were randomly assigned to receive 100 mg intramuscular tramadol, 40 ?g intranasal desmopressin, or 40 ?g intranasal desmopressin plus 100 mg intramuscular tramadol. The severity of the pain was assessed using Visual Analogue Scale. RESULTS: The studied patients consisted of 49 men and 41 women with the mean age of 35.20 Â± 13.26 years (range, 16 to 82 years). There was no statistically significant difference regarding the mean age (F [2, 89] = 2.98, P = .056) and gender differences (x2 = 3.3, df = 2, P = .19) in three groups. There was also no statistically significant difference considering pain relief in 3 studied groups (P = .2). CONCLUSION: We concluded that narcotics such as pethidine cannot be replaced by tramadol in patients with renal colic, but tramadol, desmopressin,or both in combination can reduce pethidine requirement.