The magnitude of the relationship between ambulatory care fragmentation and subsequent total health care costs is unclear. To determine the association between ambulatory care fragmentation and total health care costs. Longitudinal analysis of 15 years of data (2004-2018) from the national Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, linked to Medicare fee-for-service claims. A total of 13,680 Medicare beneficiaries who are 65 years and older. We measured ambulatory care fragmentation in each calendar year, defining high fragmentation as a reversed Bice-Boxerman Index ≥0.85 and low as <0.85. We used generalized linear models to determine the association between ambulatory care fragmentation in 1 year and total Medicare expenditures (costs) in the following year, adjusting for baseline demographic and clinical characteristics, a time-varying comorbidity index, and accounting for geographic variation in reimbursement and inflation. The average participant was 70.9 years old; approximately half (53%) were women. One-fourth (26%) of participants had high fragmentation in the first year of observation. Those participants had a median of 9 visits to 6 providers, with the most frequently seen provider accounting for 29% of visits. By contrast, participants with low fragmentation had a median of 8 visits to 3 providers, with the most frequently seen provider accounting for 50% of visits. High fragmentation was associated with $1085 more in total adjusted costs per person per year (95% CI $713 to $1457) than low fragmentation. Highly fragmented ambulatory care in 1 year is independently associated with higher total costs the following year.