Background: Several local regional anesthesia regimes have been described in the literature to reduce post-surgical pain following total knee arthroplasty (TKA), but it is unclear which regime has the best analgetic effect combined with the best motor function. The aim of this study was to determine if patients with infiltration between the popliteal artery and capsule of the posterior knee (IPACK) combined with an adductor canal block (SACB) had less pain, better motor function, and less opioid consumption after TKA than patients with a femoral nerve block (FNB) combined with a popliteal sciatic nerve block (PSB). Methods: In a retrospective cohort analysis, 342 patients following primary TKA were examined; 175 patients were treated with an IPACK combined with a SACB, and 167 patients with a femoral FNB combined with a PSB. The outcome parameters postoperative pain (visual analogue scale (VAS) for mobilization and at rest, functional recovery, opioid consumption, hospital discharge, and complications were analyzed and compared between both groups. Results: The IPACK/SACB group had a higher postoperative need for opioids despite higher doses of ropivacaine compared to the FNB/PSB group, accompanied by higher VAS scores. Patients' satisfaction was equal between the groups. Both groups showed comparable mobilization rates and walking distances following TKA. Conclusions: IPACK/SACB showed equal results compared to FNB/PSB for mobilization rates and patients' satisfaction following TKA without a reduction in opioid consumption.