Objective To compare clinical efficacy and safety of combined use of Olfen and Phenylene trihydroxybenzene with single use of the drugs in the treatment of acute renal colic. Methods Two hundreds and fifty-five patients with acute renal colic were randomly divided into three groups with 85 in each group. The combined treatment group was administrated with intramuscular injection of 95 mg Olfen and intravenous drop infusion of 80 mg Phenylene trihydroxybenzene. The Olfen control group was administrated with intramuscular injection of 95 mg Olfen and the Phenylene trihydroxybenzene control group was given intravenous drop infusion of 80 mg Phenylene trihydroxybenzene. The efficacy and the side effects were observed 10, 20, and 40 min after administration and compared between the three groups. Results At 40 min after administration, the total efficacy rate and sustained efficacy rate of the combined treatment group (95.3% and 88.9%) were higher than those of the Olfen control group (85.9% and 61.6%) and the Phenylene trihydroxybenzene control group (83.5% and 35.4%). The onset time of drug in the combined treatment group was shorter than that in the Olfen control group and the Phenylene trihydroxybenzene control group [(13.0 ± 5.2) min vs. (18.0 ± 6.0) min and (19.0 ± 7.5) min]. The pain remission duration in the combined treatment group was longer than that in the Olfen control group and the Phenylene trihydroxybenzene control group [(4.6 ± 1.5) h vs. (2.8 ± 1.6) h and (2.6 ± 1.8) h]. The adverse reaction rate in the combined treatment group was 7.1% (6/85), which was similar with that in the Olfen control group and the Phenylene trihydroxybenzene control group. Conclusions Olfen combined with Phenylene trihydroxybenzene is a safe and effective therapy for patients with acute renal colic, and is worthy of clinical application.