Spaceflight and bed rest (BR) result in loss of muscle mass and strength. This study evaluated the effectiveness of resistance training and vibration-augmented resistance training to preserve thigh (quadriceps femoris) and calf (triceps surae) muscle cross-sectional area (CSA), isometric maximal voluntary contraction (MVC), isometric contractile speed, and neural activation (electromyogram) during 60 days of BR. Male subjects participating in the second Berlin Bed Rest Study underwent BR only [control (CTR), n = 9], BR with resistance training (RE; n = 7), or BR with vibration-augmented resistance training (RVE; n = 7). Training was performed three times per week. Thigh CSA and MVC torque decreased by 13.5 and 21.3%, respectively, for CTR (both P < 0.001), but were preserved for RE and RVE. Calf CSA declined for all groups, but more so (P < 0.001) for CTR (23.8%) than for RE (10.7%) and RVE (11.0%). Loss in calf MVC torque was greater (P < 0.05) for CTR (24.9%) than for RVE (12.3%), but not different from RE (14.8%). Neural activation at MVC remained unchanged in all groups. For indexes related to rate of torque development, countermeasure subjects were pooled into one resistance training group (RT, n = 14). Thigh maximal rate of torque development (MRTD) and contractile impulse remained unaltered for CTR, but MRTD decreased 16% for RT. Calf MRTD remained unaltered for both groups, whereas contractile impulse increased across groups (28.8%), despite suppression in peak electromyogram (12.1%). In conclusion, vibration exposure did not enhance the efficacy of resistance training to preserve thigh and calf neuromuscular function during BR, although sample size issues may have played a role. The exercise regimen maintained thigh size and MVC strength, but promoted a loss in contractile speed. Whereas contractile speed improved for the calf, the exercise regimen only partially preserved calf size and MVC strength. Modification of the exercise regimen seems warranted.