Background This study was conducted to compare the effectiveness of low-dose ketamine versus ketorolac in pain control in patients with acute renal colic presenting to the emergency department (ED). Methods This is a double-blind randomized clinical trial. The initial pain severity was assessed using the numerical rating scale (NRS). Then, ketamine or ketorolac was administered intravenously at a dose of 0.6 mg/kg and 30 mg respectively. The pain severity and adverse drug reactions were recorded 5, 15, 30, 60, and 120 min thereafter. Results The data of 62 subjects in the ketamine group and 64 patients in the ketorolac group were analyzed. The mean age of the patients was 34.2 ± 9.9 and 37.9 ± 10.6 years in the ketamine and ketorolac group, respectively. There was no significant difference in the mean NRS scores at each time point, except for the 5 min, between the two groups. Despite a marked decrease in pain severity in the ketamine group from drug administration at the 5 min, a slight increase in pain was observed from the 5 min to the 15 min. The rate of adverse drug reactions, including dizziness ( P = 0.001), agitation ( P = 0.002), increased systolic blood pressure (> 140 mmHg), and diastolic blood pressure (> 90 mmHg) was higher in the ketamine group. Conclusions Low dose ketamine is as effective as ketorolac in pain management in patients with renal colic presenting to the ED. However, it is associated with a higher rate of adverse drug reactions.