Extended nocturnal home hemodialysis has gained renewed interest. However, no removal data for single/double needle (lumen) (SL and DL, respectively) or for low/high blood flow in extended dialysis are available. Therefore, we studied dialysis adequacy in different nocturnal home hemodialysis strategies. Coupling a kinetic with a dialyzer model, we calculated a reduction ratio from pre- to post-dialysis (RR) and total solute removal (TSR) of urea, methylguanidine (MG), β2-microglobulin, and phosphate. Simulations were done for dialysis with blood flow Qb350 ml/min (DL-4h), extended DL high flow with Qb350 (DL-HF-8h) and low flow with Qb175 (DL-LF-8h), and SL with Qb273 (SL-8h). Compared to DL-4h, TSR was 28–59% larger for DL-HF-8h. TSR was most increased for β2-microglobulin (18%) with DL-LF-8h, and for MG (35%) with SL-8h. Furthermore, RRs were equal (DL-LF-8h), higher (SL-8h), and even more increased (DL-HF-8h) for all studied solutes. In the home setting, DL-LF-8h and SL-8h are safe and promising strategies.