There is little information available concerning compliance with pharmacologic therapy for osteoporosis in the usual care setting. We evaluated 176 consecutive, previously untreated women whose physicians initiated treatment for osteoporosis following a bone mineral density (BMD) test obtained as part of routine medical practice. All patients were contacted >/=1 year after the initial BMD test and offered a follow-up BMD. Compliance with therapy was defined as the percent of time that a patient filled a prescription for osteoporosis treatment. Ninety-three (53%) patients received estrogen (ERT), 93 (53%) bisphosphonates, 8 (5%) calcitonin, and 17 (10%) received more than one therapy. Ninety-one of the 176 (52%) agreed to a follow-up BMD at a mean of 590 days after the first study (participants); 85 declined a follow-up BMD (refusers). Participants and refusers were similar for age, treatment patterns, and compliance with therapy. For all patients, compliance for those given bisphosphonate was similar to those given ERT (70.7% (95% CI 63.5-77.9%) versus 69.2% (95% CI 61.7-76.8%). For participants, the change in spine BMD was similar for those treated with bisphosphonate [mean increase 3.53 (+/-2.64)%/year (mean+/-SD)] and those treated with ERT [mean increase 3.00 (+/-2.75)%/year]. For those participants whose compliance with therapy was >/=66%, the mean increase in spine bone density was 3.80 (+/-2.59)%/year compared to 2.11 (+/-2.64)%/year ( p<0.005) for those whose compliance was <66%. Compliance with ERT and bisphosphonate therapy initiated in routine practice after a BMD was similar over a mean of 590 days. Compliance less than 66% with drug treatment results in suboptimal improvement in bone density.