Summary This is the first study to investigate the association between the use of selective serotonin reuptake inhibitor (SSRI)/serotonin–norepinephrine reuptake inhibitor (SNRI) and the risk of fractures using a nationwide representative cohort of ethnic Chinese. Current use of SSRI/SNRI and the co-morbidity, especially osteoporosis and history of falling, play an important role in the increased risk of fractures. Introduction This nested case–control study examines the association between the timing, intensity, and individual components of serotonergic antidepressant (including SSRIs and SNRIs) use and the risk of all-cause fracture. Methods Using the 2002–2011 Taiwan National Health Insurance Research Database, we identified patients who received at least three prescriptions of antidepressants between January 1st 2002 and December 31st 2010 as our study cohort. In the study cohort, we identify 8250 patients who had first admission for fracture and 33,000 matched controls (1:4, matched by age, sex, and cohort entry date). Multivariate conditional logistic regression was used to estimate the association between the use of serotonergic antidepressants and the risk of fracture. Results Current users of serotonergic antidepressants were associated with an increased risk of fracture (adjusted odds ratio (aOR) 1.16 95 % confidence interval 1.07–1.25). Furthermore, a higher risk of fractures was found in patients with osteoporosis (aOR 3.05 2.73–3.42) or a history of falling (aOR 6.13 3.41–11.0). The risks of fracture between SSRI and SNRI users were comparable. Conclusion Current use of SSRI/SNRI is associated with an increased risk of all caused fractures. Additionally, the co-morbidity, especially osteoporosis and a history of falling, plays an important role in the risk of fractures.