PURPOSE: Patients with multiple myeloma (MM) develop osteolytic lesions with fractures, pain, and impaired quality of life. Preclinical data show an anabolic effect of loading exercise in osteolytic lesions of MM. This 6-month pilot study evaluated feasibility and safety of impact-loading exercise in patients with MM after assessment of spinal stability. METHODS: We assigned 20 patients to perform 45 min of guided impact-loading exercise twice a week and home-based training once a week or stretching exercise twice a week. Primary endpoint was assessment of feasibility and safety. Secondary endpoints were assessments of physical performance, quality of life, and bone remineralization. RESULTS: Of 77 eligible patients with MM, 26% accepted participation. In the impact group, 9/12 and in the stretching group 7/8 patients completed training with adherence rates of 65.8 and 81.1%. Ninety percent of the stamping and jumping exercises were performed with increasing intensity from the prescribed training volume of ≥ 100%. Low severity pain events were reported after 32.9% of impact sessions. No serious adverse events were observed. After 6 months, 6-minute walk distance increased in the impact group by 35 m and in the stretching group by 46 m, and chair-rise test improved in the stretching group by 1.7 s. Global health status increased by 24.9% in the impact group, and functional scale by 31.9% in the stretching group based upon EORTC QLQ-C30. No signs of bone remineralization were observed in computed tomography. CONCLUSION: Impact training is feasible and appears to be safe in selected MM patients.