The LACE index and HOSPITAL score models are the two most commonly used prediction models identifying patients at high risk of readmission with limited information for home care patients. This study compares the effectiveness of these two models in predicting 30-day readmission following acute hospitalization of such patients in Taiwan. A cohort of 57 home care patients were enrolled and followed-up for one year. We compared calibration, discrimination (area under the receiver operating curve, AUC), and net reclassification improvement (NRI) to identify patients at risk of 30-day readmission for both models. Moreover, the cost-effectiveness of the models was evaluated using microsimulation analysis. A total of 22 readmissions occurred after 87 acute hospitalizations during the study period (readmission rate = 25.2%). While the LACE score had poor discrimination (AUC = 0.598, 95% confidence interval (CI) = 0.488-0.702), the HOSPITAL score achieved helpful discrimination (AUC = 0.691, 95% CI = 0.582-0.785). Moreover, the HOSPITAL score had improved the risk prediction in 38.3% of the patients, compared with the LACE index (NRI = 0.383, 95% CI = 0.068-0.697, p = 0.017). Both prediction models effectively reduced readmission rates compared to an attending physician's model (readmission rate reduction: LACE, 39.2%; HOSPITAL, 43.4%; physician, 10.1%; p < 0.001). The HOSPITAL score provides a better prediction of readmission and has potential as a risk management tool for home care patients.