Background <p>Cryotherapy is a non-pharmacological option that complements drug therapy to achieve the most comprehensive multimodal analgesia. Various techniques are currently available, including the conventional gel cold pack, the cryo-cuff, and a novel mobile cold compression device (MCCD). This study aimed to evaluate and compare three cryotherapy techniques in terms of efficacy and patient satisfaction in patients undergoing total knee arthroplasty (TKA).</p> Methods <p>This prospective randomized study included 108 patients who were scheduled for primary unilateral TKA. The patients were allocated to 3 groups for postoperative cryotherapy techniques: gel cold pack, cryo-cuff, and MCCD. Scores on the visual analog scale (VAS) for pain intensity, morphine consumption, knee range of motion (ROM), knee swelling, length of hospital stay, and patient satisfaction were collected.</p> Results <p>Postoperative VAS scores showed a significant difference among the groups at 8 and 72&#xa0;h after surgery (<i>P</i> = 0.002 and 0.026, respectively). At the earliest postoperative time point, post hoc analysis demonstrated that patients in the MCCD group had lower pain scores than those in the gel cold pack (<i>P</i> &lt; 0.001) and the cryo-cuff group (<i>P</i> = 0.030). However, cryo-cuff reduced knee swelling significantly compared to gel cold pack (<i>P</i> = 0.028) and MCCD (<i>P</i> = 0.011) at postoperative 72&#xa0;h. The total satisfaction score was 86.8, 82.8, and 89.1 with gel cold pack, cryo-cuff, and MCCD, respectively.</p> Conclusions <p>Cryotherapy is an adjunct to post-TKA pain control at the surgical site. MCCD has shown superior efficacy in pain reduction during the earliest postoperative period, and achieved high patient satisfaction.</p> Trial registration <p>This study was registered in the Thai Clinical Trials Registry database (no. TCTR20200517002).</p>