Long-term treatment of osteoporosis is required for optimal efficacy, but adherence to therapy is suboptimal with daily and weekly oral bisphosphonates. The aim of this study was to assess real-world persistence (long-term adherence) with weekly alendronate. Persistence data were collected according to World Health Organization criteria for the prior month and year for 102 consecutive patients with osteoporosis at three outpatient clinics in Croatia. Persistence was assessed using medication possession ratios (MPR). Adequate persistence was defined as sufficient medication supply to ensure antifracture efficacy (MPR >or=80%). Self-reported persistence data were compared with resupply prescription data from primary care physicians (PCPs). The effect of patient age, co-therapy, co-morbidity, and time since osteoporosis was diagnosed were evaluated. A diagnosis of osteoporosis was established 3.21+/-1.83 years prior for the 96 women and six men enrolled (mean age 66.92+/-8.05 years). During the previous year, 86.3% patients reported not missing any tablets. Age correlated with the number of missed tablets, with older patients missing more tablets (p=0.038). Patients with co-therapy (p=0.042) missed more tablets. PCPs reported that 65.7% of the patients were issued prescriptions for 52 tablets. A total of 68.7% had MPR >80%. Patients with rheumatoid arthritis did not impact MPR (p=0.936). Previous fractures or number of fractures were not associated with persistence (p>0.05). In Croatia, persistence was superior with weekly-administered alendronate than has been reported elsewhere, perhaps due to socio-cultural factors. Larger, longitudinal studies are needed to confirm these results.