(1) Background: Recommendation algorithms have played a vital role in the prediction of personalized recommendation for clinical decision support systems (CDSSs). Machine learning methods are powerful tools for disease diagnosis. Unfortunately, they must deal with missing data, as this will result in data error and limit the potential patterns and features associated with obtaining a clinical decision; (2) Methods: Recent years, collaborative filtering (CF) have proven to be a valuable means of coping with missing data prediction. In order to address the challenge of missing data prediction and latent feature extraction, neighbor-based and latent features-based CF methods are presented for clinical disease diagnosis. The novel discriminative restricted Boltzmann machine (DRBM) model is proposed to extract the latent features, where the deep learning technique is adopted to analyze the clinical data; (3) Results: Proposed methods were compared to machine learning models, using two different publicly available clinical datasets, which has various types of inputs and different quantity of missing. We also evaluated the performance of our algorithm, using clinical datasets that were missing at random (MAR), which were missing at various degrees; and (4) Conclusions: The experimental results demonstrate that DRBM can effectively capture the latent features of real clinical data and exhibits excellent performance for predicting missing values and result classification.