Abstract Objective To compare the improvement in disability, kinesiophobia, pain, and quality of life obtained by means of home-based functional exercises aimed at managing kinesiophobia with that obtained by giving subjects undergoing total knee arthroplasty (TKA) advice to stay active after discharge from a rehabilitation unit. Design Randomized controlled trial with 6-months’ follow-up. Setting Patients' homes. Participants Patients (N=110; 40 men; mean age, 67y) at the end of a 15-day period of in-hospital rehabilitation after undergoing primary TKA. Interventions In the experimental group, before returning home, the patients were asked to continue the functional exercises learned during hospitalization in twice-weekly 60-minute sessions for 6 months, and were given a book containing theoretical information about the management of kinesiophobia. In the control group, the patients were advised to stay active and gradually recover their usual activities. Main Outcome Measures Repeated-measures analysis of covariance with baseline values as the covariates (P<.05) was used to assess the effect of treatment on disability, fear-avoidance beliefs, pain intensity, and quality of life. Results The analysis revealed a significant time by group interaction in all the variables in favor of the experimental group. Post hoc analysis showed that the effect of the group was statistically significant at the end of home training and follow-up. The treatment effect was clinically tangible in terms of disability and quality of life, and persisted for 6 months after the intervention ended. Conclusions A home-based program based on functional exercises and the management of kinesiophobia was useful in changing the course of disability, fear-avoidance beliefs, pain, and the quality of life in patients with TKA.