Objective: Treatments against osteoporosis have demonstrated fracture risk reduction but persistence to therapy remains a major issue. Intermittent regimens have been developed to improve persistence. The aim of this 1-year prospective study was to compare, in the general population, the persistence of various oral regimens of antiosteoporotic treatment. Methods: We conducted this prospective study in the French comprehensive public health insurance database of the Rhône-Alpes region. Women aged 45 years or older who had a first reimbursement of an oral antiosteoporotic treatment during February 2007 composed the study cohort. Persistence was defined by the proportion of patients refilling a prescription in the pharmacist delivery register (ERASME). Using statistical analyses like Kaplan-Meier survival curves and log-rank tests, we compared the treatment persistence of strontium ranelate, raloxifene, and daily-, weekly-, and monthly bisphosphonates. Results: Two thousand four hundred and nineteen patients were included over a period of 1 month and followed up for 12 months. Two hundred and eighty-nine (11.9%) patients were treated with monthly bisphosphonates, 1298 (53.7%) with weekly bisphosphonates, and 832 (34.4%) with daily treatments (526 strontium ranelate (21.7%), 296 raloxifene (12.2%), and 10 bisphosphonates (0.4%)). At 1 year, overall persistence was 34%. Fifty percent of patients on monthly bisphosphonates were still persistent while only 37% of patients on weekly bisphosphonates, 34% on raloxifene, and 16% on strontium ranelate were persistent. Therapy monitoring with biochemical markers or bone mineral density was associated with improved persistence. Conclusion: Overall persistence at 1 year was low, but intermittent regimens were associated with higher persistence rates, along with women who had therapy monitoring.