Aim: To investigate the analgesic efficacy and safety of combined therapy using drotaverine and ketorolac vs ketorolac in the treatment of acute renal colic. Methods: This was a retrospective study of a consecutive cohort that included 322 emergency department (ED) patients with a diagnosis of renal colic from our hospital, from June 2014 to September 2015. Pain intensity (PI) was recorded using a visual analog scale (VAS) at different time-points after treatment. The primary outcome was defined as a decrease of 50% or more in the mean PI. The need for rescue analgesics in 120 min and occurrence of adverse effects were considered as secondary outcomes. Results: Of 322 eligible patients, 249 patients were analyzed in this study: 125 patients received ketorolac plus drotaverine and 124 patients received ketorolac only. There were significant differences in PI between the two groups at 30min and 120 min (PI: [OR 1.573, 95% Cl: 1.007-3.054, P-30 min = 0.047], [OR 2.938, 95% Cl: 1.11-7.78, P-120 min = 0.03] in multivariable logistic regression) (PI: [OR 1.869, 95% Cl: 1.119-3.121, P-30 min = 0.017], [OR 2.938, 95% Cl: 1.117.78, P-120 min = 0.03] in univariable logistic regression). Moreover, significant differences were also found in PI in subgroup analysis of patients with mid and proximal ureteric stones (PI: [OR 3.888, 95% Cl: 1.409-10.729, P-30 min = 0.009] in multivariable logistic regression) (PI: [OR 3.476, 95% Cl: 1.363-8.865, P-30 min = 0.009] in univariable logistic regression). Pain relief at 120 min was obtained in 119 patients (95.2%) receiving combined therapy and in 106 patients (85.5%) receiving ketorolac (P = 0.011). Rescue analgesics were required in six patients (4.8%) receiving combined therapy and 18 patients (14.5%) receiving ketorolac (P = 0.009). Adverse events were similar between the two groups: 20 (16%) in the combined group and 16 (13%) in the ketorolac group (P = 0.843). Conclusion: Ketorolac combined with drotaverine is effective in relief of acute renal colic, especially pain due to mid and proximal ureteric lithiasis, but did not decrease PI significantly in renal colic patients with renal and distal ureteral stones. On the other hand, combined therapy with ketorolac and drotaverine was associated with a reduced use of rescue analgesics.