Japanese government has required insurers to formulate a population health management. A cost prediction is needed to evaluate the plan. Since one insured can have multiple diseases, a traditional linear model is not appropriate for the prediction. We developed a medical cost prediction model using a statistical machine learning method. Claims data of six health insurance societies (1,009,167 insureds, average age: 34.3, female: 54%) covered in 2016 were used. Insureds were randomly divided into those for training data and validation data at a ratio of 7 to 3. Difference in logarithmic value of annual medical cost from that of demographically matched population was defined as excess logarithmic medical cost. A prediction model, a regression model with least absolute shrinkage and selection operator (LASSO), was developed using the excess logarithmic cost as explained valuables, and dummy valuables of each disease and their interaction terms as explanatory valuables. Explanatory valuables were selected by LASSO avoiding overfitting using the validation data. Excess logarithmic costs of extracted individuals (741,067) were almost normally distributed. Of the explanatory valuables, 58% were single diseases and 24%, 14%, and 4% were the interaction terms of two, three, and four diseases, respectively. Among the valuables, constipation had the highest impact on medical cost followed by insomnia, asthma bronchiale, diabetes, and low back pain. Among the interaction terms of two, insomnia and asthma bronchiale had the highest impact. The coefficient of determination of the prediction model (0.42) was higher than that of a traditional linear model (0.25). We developed a cost prediction model using machine learning. The model may be useful to assess a population health management plan. In addition, the prevalence rates of the explanatory valuables of the model may be useful for the comparison among insurers and for planning an effective population health management plan.