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Background To decrease hospital readmission rates, clinical practices create a transition of care (TOC) process to assess patients and coordinate care postdischarge. As current evidence suggests lack of universal benefit, this study's objectives are to determine what patient and process factors associate with hospital readmissions, as well as construct a model to decrease 30-day readmissions. Methods Three months of retrospective discharged patient data (n = 123) were analysed for readmission influences including: patient-specific comorbidities, admission-specific diagnoses, and TOC components. A structured intervention of weekly contact, the Care Coordination Cocoon (CCC), was created for multiply readmitted patients (MRPs), defined as ≥2 readmissions. Three months of postintervention data (n = 141) were analysed. Overall readmission rates and patient- and process-specific characteristics were analysed for associations with hospital readmission. Results Standard TOC lacked significance. Patient-specific comorbidities of cancer (odds ratio [OR] 6.27; 95% confidence interval [CI] 1.73–22.75) and coronary artery disease (OR 6.71; 95% CI 1.84–24.46), and admission-specific diagnoses within pulmonary system admissions (OR 7.20; 95% CI 1.96–26.41) were associated with readmissions. Post-CCC data demonstrated a 48-h call (OR 0.21; 95% CI 0.09–0.50), answered calls (OR 0.16; CI 0.07–0.38), 14-day scheduled visit (OR 0.20; 95% CI 0.07–0.54), and visit arrival (OR 0.39; 95% CI 0.17–0.91) independently associated with decreased readmission rate. Patient-specific (hypertension—OR 3.65; CI 1.03–12.87) and admission-specific (nephrologic system—OR 3.22; CI 1.02–10.14) factors associated with readmissions which differed from the initial analysis. Conclusions Targeting a practice's MRPs with CCC resources improves the association of TOC components with readmissions and rates decreased. This is a more efficient use of TOC resources. [ABSTRACT FROM AUTHOR]