Objective: The 75% of older adults with multiple chronic conditions are at risk of therapeutic competition (i.e. treatment for one condition may adversely affect a coexisting condition). The objective was to determine the prevalence of potential therapeutic competition in community-living older adults. Methods: Cross-sectional descriptive study of a representative sample of 5,815 community-living adults 65 and older in the U.S, enrolled 2007-2009. The 14 most common chronic conditions treated with at least one medication were ascertained from Medicare claims. Medication classes recommended in national disease guidelines for these conditions and used by ≥2% of participants were identified from in-person interviews conducted 2008-2010. Criteria for potential therapeutic competition included: 1), well-acknowledged adverse medication effect; 2) mention in disease guidelines; or 3) report in a systematic review or two studies published since 2000. Outcomes included prevalence of situations of potential therapeutic competition and frequency of use of the medication in individuals with and without the competing condition. Results: Of 27 medication classes, 15 (55.5%) recommended for one study condition may adversely affect other study conditions. Among 91 possible pairs of study chronic conditions, 25 (27.5%) have at least one potential therapeutic competition. Among participants, 1,313 (22.6%) received at least one medication that may worsen a coexisting condition; 753 (13%) had multiple pairs of such competing conditions. For example, among 846 participants with hypertension and COPD, 16.2% used a nonselective beta-blocker. In only 6 of 37 cases (16.2%) of potential therapeutic competition were those with the competing condition less likely to receive the medication than those without the competing condition. Conclusions: One fifth of older Americans receive medications that may adversely affect coexisting conditions. Determining clinical outcomes in these situations is a research and clinical priority. Effects on coexisting conditions should be considered when prescribing medications. © 2014 Lorgunpai et al.