Overactive bladder prevalence increases in older adults often complicating the management of other comorbidities. The theoretical antagonism between the parasympathetic-blocking anticholinergic agent and the parasympathetic stimulatory agents concomitantly used by patients is only recently being explored. The primary aim was to determine the frequency of the annual use of acetylcholinesterase inhibitors, overactive bladder anticholinergics, and the use of both agents in the same year. The secondary aim was measurement of the association between annual hospitalization and same-year use of both acetylcholinesterase inhibitors and anticholinergics. The US nationally representative MarketScan ® Medicare databases were analyzed. In the Medicare enrollees, there were 122 020, 141 920, and 15 639 users of acetylcholinesterase inhibitors, anticholinergics, and both agents, respectively. The percentage of acetylcholinesterase inhibitor users who also used anticholinergics was 12.8%. Comparing users of both acetylcholinesterase inhibitors and anticholinergics to those using AChEI alone, 5 608 of the former experienced a hospitalization (35.9%) compared to 33 182 of the latter (31.2%). There was an increased risk of hospitalization for those using both acetylcholinesterase inhibitors and anticholinergics in the same year, with an odds ratio (OR) of 1.23 (95% CI, 1.19, 1.28). Clinicians should consider improved monitoring of the usage of both medications and clarify alternative regimens that avoid anticholinergics in at-risk older adults.