OBJECTIVES: Oral bisphosphonate therapy reduces the risk of fractures and associated morbidity in women with post-menopausal osteoporosis. This study evaluated how failure to persist and comply with oral bisphosphonates impacts on the use of health care services and costs. METHODS: Retrospective cohort analysis of 6,870 women with incident bisphosphonate prescribing in UK primary care. Persistence was defined as no gaps in refill of >30 days; compliance was measured using medication possession ratio (MPR ≥80). The impact of non-persistence and non-compliance on the intensity of health service use (HSU) in the 24-month period following treatment was analyzed using negative binomial regression; the impact on costs was analysed using gamma regression. Primary care data, linked Hospital Episode Statistic data and nationally available prescribing and health care cost data were used.  RESULTS: Persistence and compliance in the 24-month period was 32.4% and 59.2% respectively. In multivariable analysis, non-persistent patients had a 15% increased frequency of primary care contact (incident rate ratio (IRR): 1.15; 95% CI: 1.12-1.19) and a 92% increased (IRR: 1.92; 95% CI: 1.74-2.12) frequency of inpatient hospitalisation for any cause. The IRR of osteoporosis-related hospitalisations for non-persistent patients was 2.23 (95% CI: 1.66-2.98). Non-compliant patients had a 5% increased frequency of primary care contact (IRR: 1.05; 95% CI: 1.02-1.18), a 55% increased (IRR:1.55; 95% CI: 1.41-1.69) frequency of all-cause inpatient hospitalisation and a 37% increased frequency of osteoporosis-related hospitalisations (IRR: 1.37; 95% CI:1.07 -1.75). Average total health care cost was significantly higher among non-persistent (£3,557 [95% CI: £3,372-£3,742]) than persistent patients (£2,540 [95% CI: £2,370- £2,710]). Among non-compliant patients, average total health care costs was £3,592 (95% CI: £3,369 –3,816) compared to compliant patients- £3,028 (95% CI: £2,853- £3,202)- a cost difference of £564.  CONCLUSIONS: Suboptimal persistence and compliance with oral bisphosphonates is associated with significant increases in HSU and costs.