Objective The aim of this study was to investigate whether subclinical hypothyroidism could increase the risk of postoperative complications in patients undergoing primary total knee arthroplasty (TKA). Methods A prospective case-control study of 796 patients undergoing primary TKA between January 2015 and January 2020 was performed. A total of 700 patients (87.9%) were female and the average age of included patients was 65.0 years, with a standard deviation of 5.6. The participants who had subclinical hypothyroidism were referred to as the case group, while those without abnormal thyrotropin (TSH) were included in the control group (matched for age and gender). The fasting plasma levels of TSH were tested in the morning in all patients. The diagnosis of subclinical hypothyroidism was completed by a senior endocrinologist based on laboratory tests; namely, a serum TSH >= 5 mu/L and normal free thyroxine (FT4). Subclinical hypothyroidism was further described as mild (TSH < 10 mu/L) or severe (TSH >= 10 mu/L). The incidence of 90-day postoperative complications was compared between two cohorts. Logistic regression analysis was used for the risk factors of 90-day postoperative complications following TKA. Results A total of 398 patients had a diagnosis of subclinical hypothyroidism. Among them, 275 cases (69.1%) were described as mild (79 patients [19.8%] with low FT4 and 196 patients [49.2%] with normal FT4 in the repeated test) and 123 cases (30.9%) as severe subclinical hypothyroidism. Of the 196 patients (49.2%) with mild subclinical hypothyroidism and normal FT4, 63 patients (15.8%) had symptoms before surgery. Patients were followed up for an average duration of 25.4 months (6 to 43 months). A total of 265 patients (66.6%) received preoperative treatment for subclinical hypothyroidism, with an average therapy time of 9.2 months. There were 162 patients (40.7%) with positive autoantibodies to thyroid peroxidase (anti-TPO). There were no statistically significant differences in baseline data between cohorts (all P > 0.05). As for the cumulative 90-day outcomes, subclinical hypothyroidism increased the incidences of both medical and surgical complications following primary TKA compared to those without this condition (11.6% vs 7.2%, OR = 1.55, 95% confidence interval [CI] = 1.47-1.62, P < 0.05). Subclinical hypothyroidism caused patients to suffer increased total incidence of readmission within the first 90 days after discharge when compared to those without this condition (20.61% vs 14.15%, OR = 1.45, 95% CI = 1.41-1.49, P < 0.001). Controlling for preoperative and intraoperative variables, the patients with TSH >= 10 mu/L and positive anti-TPO and those without corrected subclinical hypothyroid and thyroid hormone supplementation were more likely to experience postoperative complications within 90 days of TKA. Conclusion Subclinical hypothyroidism might increase the risk of postoperative complications within 90 days of TKA, especially for the patients with TSH >= 10 mu/L and positive anti-TPO and those without corrected subclinical hypothyroid and thyroid hormone supplementation.