Background. Studies of drug-related hospitalizations have focused on adverse drug reactions, but few data are available on therapeutic failures (TFs) and adverse drug withdrawal events (ADWEs) leading to hospitalization among community-dwelling older adults. Thus, we sought to describe the prevalence of unplanned hospitalizations caused by TFs and ADWEs. In addition, we evaluated factors associated with these events in a nationally representative sample of older Veterans. Methods. This study included 678 randomly selected unplanned hospitalizations of older (age ≥ 65 years) Veterans between December 1, 2003, and November 9, 2006. The main outcomes were hospitalizations caused by a TF and/or an ADWE as determined by a pair of health professionals from review of medication charts and application of the Therapeutic Failure Questionnaire and/or Naranjo ADWE algorithm, respectively. Preventability (ie, medication error) of the admission was also assessed. Results. Thirty-four TFs and eight ADWEs involving 54 drugs were associated with 40 (5.9%) Veterans' hospitalizations; of these admissions, 90.0% (36/40) were rated as potentially preventable mostly due to medication nonadherence and suboptimal prescribing. The most common TFs that occurred were heart failure exacerbations (n = 8), coronary heart disease symptoms (n = 6), tachyarrhythmias (n = 3), and chronic obstructive pulmonary disease exacerbations (n = 3). Half (4/8) of the ADWEs that occurred were cardiovascular in nature. Multivariable logistic regression modeling indicated that black Veterans (adjusted odds ratio 2.92, 95% CI 1.25-6.80) were significantly more likely to experience a TF-related admission compared with white Veterans. Conclusions. TF-related unplanned hospitalizations occur more frequently than ADWE-related admissions among older Veterans. Almost all TFs and/or ADWEs are potentially preventable.