Objective The aim of the study is to evaluate the acute responses, in the in-hospital setting, of intensive elastic resistance training on physical function, pain, psychosocial variables, and inflammatory markers in patients undergoing total knee arthroplasty. Design In a randomized controlled trial, 40 patients with total knee arthroplasty (≥55 yrs) were assigned to either (1) the intervention group (elastic resistance strengthening) or (2) a control group (conventional protocol). Patients performed three sessions in the hospital at 24, 48, and 72 hrs after total knee arthroplasty. Outcome measures included: self-administered physical function, pain intensity, kinesiophobia, catastrophizing, self-efficacy, range of motion, perceived change, test timed up and go, knee joint effusion, isometric strength, pressure pain thresholds, and inflammatory markers (levels of procalcitonin and C-reactive protein). Results The mixed analysis of variance model showed a significant group*time interaction in favor of the intervention group with a large effect size for kinesiophobia (ηp² = 0.308, P < 0.001), catastrophizing (ηp² = 0.242, P < 0.001), and passive range of motion flexion (ηp² = 0.167, P < 0.001) and a moderate effect size for physical function (ηp² = 0.103, P = 0.004), pain intensity (ηp² = 0.139, P < 0.001), timed up and go (ηp² = 0.132, P = 0.001), self-efficacy (ηp² = 0.074, P = 0.016), active range of motion flexion (ηp² = 0.121, P = 0.002), levels of procalcitonin (ηp² = 0.099, P = 0.005), and C-reactive protein (ηp² = 0.106, P = 0.004). Conclusions Three sessions of intensive elastic resistance training improve physical function, perceived pain, psychosocial variables, and inflammatory markers during the hospitalization period after total knee arthroplasty.