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Fast-track surgery is a multimodal evidence-based approach to perioperative care aimed at reducing complications and recovery time. We compared a fast-track protocol to standard care in the setting of a small Italian general hospital. Propensity score estimation before and after the study was performed to compare pre-fast-track (pre-FT; January 2013–March 2014) and fast-track (FT; January 2016–December 2016) patients undergoing elective hip and knee replacement surgery with a three-year follow-up (up to January 2020). The primary endpoints were the mean hemoglobin drop, mean predischarge hemoglobin, transfusion and reinfusion rates, pain, ambulation day, hospital length of stay (LOS), and discharge to home/outpatient care or rehabilitation hospital center. The secondary endpoints were the adherence measures to the FT protocol, namely, tourniquet and surgical times, use of drains and catheters, type of anesthesia administered, and complications within three years. The risk difference (RD) and the adjusted odds ratio (aOR) were calculated for each outcome. After the propensity score estimation, we analyzed 59 patients in the pre-FT and 122 in the FT categories. The FT patients, with respect to the pre-FT patients, ameliorated their mean hemoglobin drop from 3.7 to 3.1 g/dl (p < 0.01) and improved their predischarge mean hemoglobin (10.5 g/dL versus 11.0 g/dL; p = 0.01). Furthermore, the aOR of being transfused was reduced by 81% (p < 0,01); the RD of being reinfused was reduced by 63% (p < 0.01); the aOR of having low pain on the first day was increased by more than six times (p < 0.01); the RD of ambulating the first day increased by 91% (p < 0.01); the aOR of admission to a rehabilitation hospital center was reduced by 98% (p < 0.01); the aOR of home discharge increased by 42 times (p < 0.01); the median LOS, tourniquet and surgical times, and use of catheters and drains significantly decreased. Patients with complications at 1 month were 43.1% and 38.2%, respectively, of pre-FT and FT patients (p = 0.63). Complications at 6, 12, 24, and 36 months were significantly lower for the FT patients. This study showed that the uptake of enhanced recovery practices was successful and resulted in the improvement of clinical and organizational outcomes. The fast-track concept and related programs may optimize perioperative care and streamline surgical and rehabilitation care paths. [ABSTRACT FROM AUTHOR]