Optimal osteogenic mechanical loading requires the application of high-magnitude strains at high rates. High-intensity resistance and impact training (HiRIT) applies such loads but is not traditionally recommended for individuals with osteoporosis because of a perceived high risk of fracture. The purpose of the LIFTMOR trial was to determine the efficacy and to monitor adverse events of HiRIT to reduce parameters of risk for fracture in postmenopausal women with low bone mass. Postmenopausal women with low bone mass (T-score < –1.0, screened for conditions and medications that influence bone and physical function) were recruited and randomized to either 8 months of twice-weekly, 30-minute, supervised HiRIT (5 sets of 5 repetitions, >85% 1 repetition maximum) or a home-based, low-intensity exercise program (CON). Pre- and post-intervention testing included lumbar spine and proximal femur bone mineral density (BMD) and measures of functional performance (timed up-and-go, functional reach, 5 times sit-to-stand, back and leg strength). A total of 101 women (aged 65 ± 5 years, 161.8 ± 5.9 cm, 63.1 ± 10.4 kg) participated in the trial. HiRIT (n = 49) effects were superior to CON (n = 52) for lumbar spine (LS) BMD (2.9 ± 2.8% versus –1.2 ± 2.8%, p < 0.001), femoral neck (FN) BMD (0.3 ± 2.6% versus –1.9 ± 2.6%, p = 0.004), FN cortical thickness (13.6 ± 16.6% versus 6.3 ± 16.6%, p = 0.014), height (0.2 ± 0.5 cm versus –0.2 ± 0.5 cm, p = 0.004), and all functional performance measures (p < 0.001). Compliance was high (HiRIT 92 ± 11%;​ CON 85 ± 24%) in both groups, with only one adverse event reported (HiRIT:​ minor lower back spasm, 2/70 missed training sessions). Our novel, brief HiRIT program enhances indices of bone strength and functional performance in postmenopausal women with low bone mass. Contrary to current opinion, HiRIT was efficacious and induced no adverse events under highly supervised conditions for our sample of otherwise healthy postmenopausal women with low to very low bone mass.