Outer ear infections (OEs) affect millions of people annually with significant associated healthcare costs. Incorrect administration or noncompliance with the treatment regimen can lead to infection persistence, recurrence, antibiotic resistance, and in severe cases, aggravation to malignant otitis externa. Such issues are particularly pertinent for military personnel, patients in nursing homes, the geriatric population, patients with head or hand tremors, and those with limited or no access to proper healthcare. With the intent of using traditional material science principles to deconvolute material design while increasing relevance and efficacy, we developed a single application, cold-chain independent thixotropic drug delivery system. This can be easily applied into the ear as a liquid and then gels to deliver effective concentrations of antibiotics against bacterial strains commonly associated with OEs. The system maintains thixotropic properties over several stress/no stress cycles, shows negligible swelling and temperature dependence, and does not impact the minimum inhibitory concentration or bactericidal effects of relevant antibiotics. Moreover, thixogels are biocompatible and are well tolerated in the ear. This drug delivery system can readily translate into a user-friendly product, could improve compliance via a single application by the diagnosing healthcare provider, and is expected to effectively treat OEs and minimize the development of antibiotic resistance, infection recurrence, or exacerbation.