Numbers of knee replacement surgeries have been rising over the past years. After having ameliorated operation techniques and material, pain management and anesthetic methods have come into focus. All 15326 patients included had undergone primary knee arthroplasty within this multicenter cohort-study, conducted in 46 orthopedic departments. Parameters were evaluated on first postoperative day. Primary outcome values were pain levels (activity, minimum and maximum pain, and pain management satisfaction). Pain medication necessity was analyzed. Parameters were compared between the types of anesthesia used: general, regional and combination anesthesia. Pain scores and pain management satisfaction were significantly better in the groups of either spinal or peripheral anesthesia combined with general anesthesia (p < 0.001, respectively). Patients who received the combination of general and spinal anesthesia were associated with the lowest need for opioids (p < 0.001). The use of a combined general and spinal anesthesia as well as using a combination of general and peripheral anesthesia in knee arthroplasty was associated with a highly significant advantage to other anesthetic techniques regarding perioperative pain management in daily clinical practice, but maybe below clinical relevance. Furthermore they were associated with positive tendency considering side effects and subjective well-being parameters.