Introduction: Knee osteoarthritis is one of the common causes leading to musculoskeletal disability of the elderly around the world. Total knee replacement (TKR) is an effective and common treatment for end stage knee arthritis. Most papers suggest that early rehabilitation could improve postoperative knee function. However, postoperative pain and local swelling are the complications that diminish range of motion (ROM) and inhibit patients’ recovery. A comprehensive review of the literature reveals that cryotherapy is an effective and safe method to overcome these complications. In this paper, a guideline of using cryotherapy in reducing postoperative pain and knee swelling so as to improve the ROM of patients and promote recovery after TKR has been developed. Objectives: The objectives of this translational research are: (1) to look for relevant papers that related to cryotherapy in reducing postoperative pain and knee swelling so as to improve the ROM of patients after TKR; (2) to gather and criticize the data obtained; (3) to develop a guideline of using cryotherapy in reducing pain, knee swelling and improving ROM of patients after TKR based on the evidence from the reviewed literature; (4) to assess the implementation potential of the newly developed guidelines; and (5) to establish the implementation and evaluation plans for the new innovation. Methods: An empirical literature search published from 2001 to 2011 by several searching engines regarding cryotherapy in reducing postoperative pain and knee swelling with the aim to improve the ROM of patients after TKR has been conducted. After that, the qualities of relevant studies were retrieved and criticized by using the appraisal checklist of the SIGN (2004). The derived evidences were then be summarized and synthesized. An evidence-based guideline was established with reference to the evidence from the reviewed literatures and the results of the quality assessment. Recommendations are graded by SIGN (2004). The implementation potential including transferability, feasibility and cost-benefit ratio of the innovation were assessed as well. Lastly, implementation and evaluation plans have been developed to assess and appraise the effectiveness of the new guideline. Results: Finally, seven studies were chosen as final references after methodological quality assessment. Four main types of comparison were made from these seven reviews including: (1) continuous compressive cryotherapy vs. compressive crepe bandage; (2) comparison in different temperature of cryotherapy; (3) outcome measures; and (4) complications in cryotherapy. After the summary, six main categories of recommendations were synthesized: (1) continuous compression cryotherapy; (2) effective temperature; (3) potential complications; (4) regular assessment; (5) duration; and (6) intermitted ice pack regimen. Based on these syntheses and recommendations, a guideline of using cryotherapy for patients after having TKR was developed. Conclusion: With the implementation of the newly developed evidence-based cryotherapy guidelines for patients after having TKR in local clinical settings, the improvement in the ROM of the knee joint will be anticipated as a result of the reduction in postoperative pain and knee swelling.