Infusions of aminobisphosphonates are now established therapies ofpostmenopausal osteoporosis. Their use is associated with fever and musculoskeletal pain in some subjects, referred to as the acute phase response (APR). The purpose of the study was to explore tolerability of zoledronic acid in the treatment of postmenopausal osteoporosis. In a 36-month open label, prospective study patients with postmenopausal osteoporosis iv received zoledronic acid at a dose of 5 mg every 12 months. We then analyzed the tolerability of the treatment at the hospital and via telephone interviews during the next 14 days and every 3 months after the infusion. Prevention of APR was carried out with paracetamol 500 mg x 3 times a day on the day of first infusion and the next 2 days. Symptoms of APR were recorded in 39% (n=43) of patients with prevention therapy. APR developed in the first 12-24 hours after infusion of zoledronic acid. Among women without prevention APR developed in 65% (n=75) of cases. (OR=0.34 CI (0.2-0.59)). After the 2 nd infusion symptoms of APR were noted in 27.9% (n=26) (р<0.05) of 93 patients, after the 3 rdin 6.6% (n=2) of 30 patients. Thus, in >90% of cases the symptoms were of mild or moderate severity, with resolution within 3 days after infusion of zoledronic acid. The most frequent symptoms were bone and muscular manifestations and a flu-like syndrome (p<0.05). APR developed during the first 12-24 hours after infusion of zoledronic acid. ARR developed 2.5 times more often in the cases when zoledronic acid was used for the first time. If paracetamol treatment was administered, APR cases were documented 1.7 times less often with lesser degree and length of manifestations. Frequency of APR dropped after repeated zoledronic acid infusions.