Background Periarticular multimodal drug injection (PMDI) is a safe and effective pain management technique after anterior cruciate ligament reconstruction (ACLR); however, adding morphine and epinephrine sometimes causes adverse effects. Therefore, we evaluated the efficacy of PMDI without morphine and epinephrine after ACLR. Methods This retrospective matched case-control study included patients who had undergone primary double-bundle ACLR with PMDI and were then matched one-to-one with a control group without PMDI based on sex, age, and body mass index using propensity-matched analysis. The following clinical outcomes were compared between the groups: visual analog scale (VAS) score, C-reactive protein (CRP) concentration, number of times the patients used additional analgesics, complication rate, and postoperative time to achieve straight leg raise (SLR). Results Twenty-nine patients with PMDI and 29 controls were enrolled. The VAS score at 1 day postoperatively was lower in the PMDI than the control group (1.93 ± 1.44 vs. 3.41 ± 1.75, respectively; P < 0.001). The CRP concentration at 1 and 3 days was lower in the PMDI than the control group (0.46 ± 0.47 vs. 1.00 ± 0.69 mg/dL, P < 0.001; and 1.93 ± 1.71 vs. 4.01 ± 2.55 mg/dL, P < 0.001, respectively). The average number of additional analgesics used was significantly lower in the PMDI than the control group. There were no significant differences in the frequency of occurrence of postoperative complications between the two groups. The number of patients who could achieve SLR within 1 day was 27/29 (93%) in PMDI group, which was significantly higher than the control group (12/29, 41%) ( P < 0.001). Conclusion PMDI without morphine and epinephrine after ACLR reduced patients’ subjective pain level, objective inflammatory response without complications and enabled patients to achieve early functional recovery.