Background and objectives: Cryotherapy is a method of treatment using cold application. This study aimed to evaluate postoperative clinical and hematological parameters and pain associated with total knee arthroplasty in patients and compared cryotherapy to the conventional method of cold ice pack compressions. Materials and Methods: Between January 2015 and January 2016, 90 patients who underwent total knee arthroplasty for grade 4 gonarthrosis were prospectively evaluated. The patients were divided into three groups (n = 30, each): Group 1, cryotherapy was applied in the pre- and postoperative periods; Group 2, cryotherapy was applied only in the postoperative period; and Group 3 (control group), only a cold pack (gel ice) was applied postoperatively. In all groups, pre- and postoperative evaluations at 6, 24, and 48 h, hemorrhage follow-up, knee circumference measurement, visual analog scale pain score, knee circumference, and temperature measured by thermal camera were recorded. Results: Of the 90 patients, 10% were men and 90% were women. The mean age was 64.3 ± 8.1 (range: 46–83) years. The patella upper end diameter values were significantly lower in the postoperative period in Groups 1 and 2 than in Group 3 (p = 0.003). Hemoglobin levels at 24 and 48 h postoperatively were significantly lower in Group 3 than in Group 1 (p < 0.001, each) and Group 2 (p = 0.038, p < 0.001). At 6, 24, and 48 h follow-ups, pain values were significantly lower in Group 2 than in Group 3 (p < 0.001). Preoperative 6, 24, and 48 h temperature values were significantly lower in Group 1 than in Group 3 (p < 0.001 for each). It was found that the difference between preoperative and postoperative knee flexion measurements was significantly different in both groups or the difference between the groups was changed in each period (p < 0.001). Conclusions: Postoperative cryotherapy is a potentially simple, noninvasive option and beneficial for the reduction of reducing pain, bleeding, length of stay, analgesic requirement and swelling after total knee arthroplasty. Moreover, there was no early or late prosthesis infection in cryotherapy groups, which may be considered as an additional measure to prevent prosthesis infection.