Investigations into the effects of bone‐targeted exercise programs on musculoskeletal health and function in men are limited. The purpose of the Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR‐M) trial was to examine the efficacy and safety of two novel, supervised, eight‐month, twice‐weekly exercise programs in middle‐aged and older men with low BMD. Men with low proximal femur and/or LS BMD were recruited and randomized to high‐intensity progressive resistance and impact training (HiRIT) or machine‐based isometric axial compression (IAC). Intervention responses were compared with those of a non‐randomized matched control group (CON). Outcomes included: proximal femur and LS BMD; calcaneal ultrasound parameters; anthropometry; body composition; physical function (timed up‐and‐go [TUG], five‐times sit‐to‐stand [FTSTS]); muscle strength (back [BES] and leg extensor strength [LES]); compliance and adverse events. Ninety‐three men (67.1±7.5yrs; 82.1±11.6kg; 175.2±6.7cm; FN T‐score ‐1.6±0.6) were recruited, and randomized to HiRIT (n=34) or IAC (n=33), or allocated to CON (n=26). HiRIT effects were superior to CON for trochanteric BMD (2.8±0.8%; ‐0.1±0.9%, p=0.024), LS BMD (4.1±0.7%; 0.9±0.8%, p=0.003), broadband ultrasound attenuation (2.2±0.7%; ‐0.8±0.9%, p=0.009), stiffness index (1.6±0.9%; ‐2.0±1.1%, p=0.011), lean mass (1.5±0.8%; ‐2.4±0.9%, p=0.002), TUG, FTSTS, BES and LES (p<0.05). IAC improved lean mass (0.8±0.8%; ‐2.4±0.9%, p=0.013) and FTSTS (‐4.5±1.6%; 7.5±2.0%, p<0.001) compared with CON. HiRIT was superior to IAC for LS BMD (4.1±0.7%; 2.0±0.7%, p=0.039), stiffness index (1.6±0.9%; ‐1.3±0.9%, p=0.025), and FTSTS (‐10.7±1.6%; ‐4.5±1.7%, p=0.010). Compliance was high in both exercise groups (HiRIT 77.8±16.6%; IAC 78.5±14.8%, p=0.872). There were five instances of minor musculoskeletal discomfort (HiRIT n=2; IAC n=3). Findings suggest HiRIT was well tolerated, and provides a more positive stimulus to bone and functional indices of falls and fracture risk compared with CON and IAC. High compliance suggests HiRIT is acceptable and feasible. Findings will facilitate development of an optimal exercise prescription for men with low BMD.