To evaluate the economic burden of treating skeletal-related events (SREs) in prostate cancer (PC) patients with bone metastasis from an insurer perspective.We conducted a retrospective cohort analysis using claims data. PC patients with bone metastasis were identified in the MarketScan Databases between January 1, 2004, and March 1, 2014. The propensity score matching approach was used to match patients with SREs to those without SREs. A pseudo-SRE date was assigned to the control group. We compared 6-month and 12-month total costs of patients between two groups after the SRE or pseudo-SRE date. All costs were adjusted to 2014 US$.We identified 4083 PC men with bone metastasis, from which 787 patients with SREs were matched (1:1) to those without SREs. On average, the total 6-month cost of treating patients with SREs was $43,746 compared with $25,956 in the matched control cohort (P < 0.05). The largest proportion of differences in costs between the two groups was incurred in the first month after the SRE index date or the pseudo-SRE date ($14,979 vs. $4,849; P < 0.05) and was mostly attributable to outpatient visits (43.4%; P < 0.05) and inpatient hospitalization (33.1%; P < 0.05). The total cost per patient over the 12-month period was $22,171 higher among patients with SREs than among patients without SREs (P < 0.05).Our findings suggest that SREs impose considerable burden on health resource utilization for payers. Costs attributable to SREs were substantial. Most costs were incurred in the first month after the occurrence of SREs. Although costs decreased thereafter, they remained significantly higher for patients with SREs in subsequent months compared with patients without SREs.