BackgroundHand infections are heterogeneous, and some may undergo successful outpatient management. There are no strict guidelines for determining which patients will likely require inpatient admission for successful treatment, and many patients succeed with outpatient therapy. We sought to determine risk factors for failed outpatient management of cellulitic hand infections.MethodsWe performed a retrospective review of patients who presented to the Emergency Department (ED) for hand cellulitic infections over five years, from 2014 to 2019. Vital signs, lab markers, Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Measure (ECM), and antibiotic use were investigated. Discharge from the ED without subsequent admission was considered an outpatient success, while admission within 30 days of the prior visit was considered a failure. Continuous variables were compared with Welch's t test, and categorical data with Fisher's exact tests. Multivariable logistic regression was performed on comorbidities. Multiple testing adjustment was performed on p-values to generate q-values.ResultsOutpatient management was attempted for 1,193 patients. 31 (2.6%) infections failed treatment, and 1,162 (97.4%) infections succeeded. Attempted outpatient treatment was 97.4% successful. Multivariable analysis demonstrated higher odds of failure with renal failure according to both CCI (OR 10.2,p< 0.001,q= 0.002) and ECM (OR 12.63,p= 0.003,q= 0.01) and with diabetes with complications according to the CCI (OR 18.29,p= 0.021,q= 0.032).ConclusionsOutpatient treatment failure was higher in patients with renal failure and complicated diabetes. These patients require a high index of suspicion for outpatient failure. These comorbidities should influence consideration for inpatient therapy though most patients can undergo successful treatment as outpatients.Level of evidenceLevel III.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13018-023-03911-5.