Among 95,057 patients >= 50 years with new antiosteoporosis medications (AOM) (2001-2013) in primary care, 1-year cessation was 51% (28%-68%), higher in men, smokers, patients with missing lifestyle data, and out normal BMI, and lower in those aged 60-79, with recent fractures or other anti-osteoporotics, suggesting non-severe osteoporosis and less risk awareness. Purpose Low compliance to anti-osteoporosis medications (AOM) has been previously reported. We aimed to estimate 1-year cessation rates of different AOMs as used in Spanish healthcare settings, and to identify associated risk factors. Methods A cohort study was performed using primary care records data (BIFAP). Patients entered the cohort when aged 50 years in 2001-2013, with >= 1 year of data available, and identified as incident users of AOM (1-year washout). Participants were divided into six cohorts: alendronate, other oral bisphosphonates, selective oestrogen receptor modulators, strontium ranelate, teriparatide, and denosumab. Patients were followed from therapy initiation to the earliest of cessation (90-day refill gap), switching (to alternative AOM), loss to follow-up, death, or end of 2013. One-year therapy cessation was estimated using life tables. Hazard ratios (of cessation) according to age, sex, lifestyle factors, morbidity, and co-medication were estimated after stepwise backwards selection. Results A total of 95,057 AOM users were identified (91% women; mean age 68). One-year cessation was 51% overall, highest for strontium ranelate (68%), and lowest for denosumab (28%). Cessation probability was higher in men (14% to 2.1-fold), smokers (>6%), and patients with missing BMI (19-28%) or smoking (6-20%) data, and overweight/obese/underweight (7% to 2.6-fold increase compared to normal weight). Patients aged 60-79 years, with a recent fracture or other drugs used for osteoporosis, had better persistence. Conclusions Over half of the patients initiating AOM stopped therapy within the first year after initiation. The described risk factors for cessation could be proxies for non-severe osteoporosis, and/or disease/risk awareness, which could inform the targeting of high-risk patients for monitoring and/or interventions aimed at improving persistence.