Total knee arthroplasty (TKA) is among the most commonly performed orthopedic procedures. Controlling the pain of this patient population is essential in improving outcomes such as opioid consumption, hospital length of stay, overall function, and rehabilitation participation following their procedure. Local anesthetic infiltration of the interspace between the popliteal artery and capsule of the posterior knee, known as the IPACK block, combined with an adductor canal block (ACB) can be used to reduce pain in the challenging area of the posterior knee after knee surgery without compromising motor function of the quadriceps muscles. One limiting factor to this combination of techniques is the duration of analgesia provided. This case series demonstrates the combination of dexmedetomidine and dexamethasone (Dex-Dex) as local anesthetic adjuvants to significantly prolong the analgesic duration of ACB (in addition to IPACK block) in three patients undergoing TKA. Preoperative ACB and IPACK blocks were performed for postoperative analgesia in three TKA patients. The anesthetic mixture was 10 cc 0.2% ropivacaine combined with 25 mcg of dexmedetomidine and 5-mg preservative-free dexamethasone for the ACB, and 0.2% ropivacaine combined with 5-mg preservative-free dexamethasone was utilized for the IPACK block. Two of the patients reported experiencing four days of analgesia and one patient reported five days of analgesia following the ACB + IPACK block. Two of the patients required no opioid analgesics postoperatively. An ACB utilizing 0.75% ropivacaine has been demonstrated to provide approximately 10.8 hours of analgesia. Our series demonstrates a significantly prolonged duration of analgesia from this injectate combination. Few studies have utilized the Dex-Dex combination. The combination, however, was previously proven to safely increase the analgesic duration of a caudal block prior to hypospadias surgeries in pediatrics. More studies are needed to understand a potential synergistic effect of Dex-Dex, which could have a substantial impact on postoperative analgesia for TKA patients.