Background and purpose: Renal colic (RC) is observed in the urinary system and known with sudden and serious pain. Various analgesics are usually used for alleviating pain in the emergency department. This study compared the effect of Propofol with Fentanyl in controlling acute RC of patients admitted to the hospital. Methods: In this study, 150 patients referred to Shahid Mohammadi Hospital (Bandar Abbas-Iran) for the treatment of RC were selected. The basal pain values of the patients were investigated by the Visual Analogue Scale (VAS) that were in range from 0 up to 10 at the 0th, (immediately before drug administration), 15th, and 30th minutes. The zero value shows lack of pain and highest value (10) means the severe pain. Results: The results showed that VAS value was significantly higher in VAS0 compared to VAS10 and VAS30 for all the groups (P<0.05). The results also showed a significant difference between Morphine, Propofol and Fentanyl for VAS10 and VAS30 (P<0.05). The results showed that values for VAS were 3.66, 1.19 and 5.05 for Morphine, Fentanyl and Propofol groups, respectively. The values for VAS30 were 2.85, 1.19 and 3.52 for Morphine, Fentanyl and Propofol groups, respectively. The lowest value was observed for Fentanyl and the highest value was observed in Propofol group for VAS10 and VAS30. Conclusion: The best response was observed in Fentanyl group and it can be recommended using Fentanyl for controlling acute renal colic and its hydronephrosis in patients admitted to the hospital.