This study aimed to compare the efficacy and safety of very early preemptive meloxicam, early preemptive meloxicam, and postoperative meloxicam administration for postoperative pain relief in patients undergoing arthroscopic knee surgery (AKS). Three hundred and six patients about to receive AKS were consecutively enrolled in this randomized, controlled study and randomly allocated into three groups: very early analgesia (VEA) group, early analgesia (EA) group, and postoperative analgesia (PA) group. Pain visual analog scale (VAS) score at rest and at flexion, patient global assessment (PGA) score, consumption of rescue pethidine, and adverse events (AEs) were assessed. Pain VAS score and severity at rest/flexion were all decreased in the VEA group compared with EA group and PA group at 4 h post-operation and were also reduced in the VEA and EA groups compared with the PA group at 8 h and 12 h post-operation. PGA score was lower in the VEA group compared with the EA group and PA group at 4 h post-operation, and was attenuated in the VEA group and the EA group compared with the PA group at 8 h, 12 h, and 24 h post-operation as well. Consumption of rescue pethidine was less in the VEA group than that in the PA group. In addition, no difference in the incidence of AEs was found among the VEA, EA, and PA groups. In conclusion, preemptive meloxicam is more effective in postoperative pain control and equally tolerated compared with postoperative meloxicam in patients receiving AKS.