Few studies have assessed the use of low-molecular weight heparins for anticoagulation during extended hemodialysis sessions. This study aimed to evaluate the efficacy of a single-bolus of tinzaparin for anticoagulation of the extracorporeal circuit and dialyzer in 8-hour hemodialysis sessions. This single-center study included all patients who underwent a single 8-hour simulation session as part of their nocturnal home hemodialysis training between 2009 and 2020. Tinzaparin was delivered as a single bolus injection at time 0 with dosing based on doubling of standard 4-hour session dose. Tinzaparin efficacy was examined via visual observations (score 1-4) of the dialyzer and venous bubble trap at the end of dialysis, and using anti-Xa measured at 15-, 30-minute and 1-, 2-, 4-, 6-, 8-hour after hemodialysis start. Forty-seven patients were included. Mean tinzaparin dose was 107 ± 20 IU/Kg. Anti-Xa levels peaked at 15-minutes with 1.3 ± 0.4 IU/mL and progressively declined reaching 0.9 ± 0.3 IU/mL at 1-hour, 0.4 ± 0.21 IU/mL at 4-hour, and 0.15 ± 0.15 IU/mL at 8-hour. After the 8-hour session, none of the patients had severe clotting of their dialyzer or venous chamber. Moderate blood clotting was observed in the dialyzer of 6 (20%) patients and in the venous chamber of 22 (61%) patients. Based on the simulation results, tinzaparin dose was increased in 27 (58%) patients with a mean home-discharge dose of 123 ± 28 IU/Kg. This study shows that anti-Xa levels stabilized rapidly after administration on tinzaparin for 8-hour hemodialysis. Administration of a single bolus tinzaparin at the start of an 8-hour dialysis session appeared effective, although dose adjustment may be required.