In working memory (WM), successful maintenance of information is affected by interference. Older adults may be especially susceptible to the effects of interference, which may cause age-related cognitive impairments. A relative score of IC was derived from cross-sectional (n = 869) and longitudinal (n = 443) data to investigate (1) if IC is reduced in normal aging, (2) if individual differences in IC related to individual performance in other cognitive domains, and (3) if 5-year change in IC is related to change in general cognition. Older age was associated with reduced IC, but no decline in IC occurred over 5 years. Also, the ability to control interference in WM was related to performance in episodic memory, verbal fluency, and block design. We also found that IC mediates the relationship between age and cognition, suggesting that age-related cognitive decline is linked to IC. Finally, we demonstrate that change in IC was related to decline in episodic memory.