BACKGROUND: Osteoporosis treatments reduce fracture risk but cannot fully eliminate it, and the concept of treatment failure (TF) or inadequate clinical response (ICR) remains debated. AIMS: The TAILOR study aims to assess the prevalence of ICR and TF in osteoporotic women undergoing active drug treatment for postmenopausal osteoporosis. METHODS: TAILOR is a retrospective study conducted in an Italian outpatient service. We included 415 patients with at least 12 months of treatment and up to 10 years, examining clinical characteristics predicting TF and ICR. TF was defined as the occurrence of two fragility fractures while on treatment or one fracture plus lack of variation BMD and ICR as the occurrence of a new osteoporotic fracture in treated patients according to previous literature. RESULTS: Seventy-two patients experienced fractures during the follow-up, of those, 26 (36%) were classified as TF. The clinical characteristics of patients with fractures were similar to those without, except for a longer postmenopausal period and lower lumbar spine bone mineral density (BMD). Postmenopausal period was significantly longer in TF compared to ICR patients. However, no significant differences were found in baseline fractures, prescribed treatments, or fracture-free survival curves with age, postmenopausal period, BMD, and previous treatments. The clinical follow-up was longer in ICR and TF patients. DISCUSSION: TAILOR shows a higher prevalence of ICR and TF (17.3%) compared to randomized controlled trials and real-world data, with 36% of fractures during follow-up classified as TF. Clinician decisions often led to changes in antiosteoporosis treatment, particularly in TF cases, though TF diagnosis was rarely cited explicitly in medical records. CONCLUSION: TAILOR emphasizes that common clinical factors do not reliably predict ICR and TF. The findings highlight the complexity of determining an algorithm for the best treatment approach to prevent TF and ICR.