Holter electrocardiography (ECG) assists in the diagnosis of arrhythmias. Its use in the inpatient setting has been described solely for the evaluation of stroke and syncope. Our aim was to assess its diagnostic value for other conditions in the internal medicine department. We included all hospitalized patients between 2018 and 2021 in a tertiary referral center. The primary outcome was a diagnostic Holter recording a new arrhythmia that led to a change in treatment. Overall, 289 patients completed a 24-h inpatient Holter ECG for conditions other than syncope or stroke, with 39 (13%) diagnostic findings. The highest diagnostic value was found in patients admitted for pre-syncope (19%), palpitations (18%), and unexplained heart failure exacerbation/dyspnea (17%). A low diagnostic yield was found for the evaluation of chest pain (5%). Heart failure with preserved ejection fraction (adjusted OR 2.3, 95% CI 1.1–5.4, p = 0.04), and baseline ECG with either a bundle branch block (AOR 4.2, 95% CI 1.9–9.2, p < 0.01) or atrioventricular block (first or second degree, AOR 5, 95% CI 2.04–12.3, p < 0.01) were among the independent predictors for a diagnostic test. Inpatient Holter ECG monitoring may have value as a diagnostic tool for selected patients with conditions other than syncope or stroke.