The problem of missing data, particularly for dichotomous variables, is a common issue in medical research. However, few studies have focused on the imputation methods of dichotomous data and their performance, as well as the applicability of these imputation methods and the factors that may affect their performance. In the arrangement of application scenarios, different missing mechanisms, sample sizes, missing rates, the correlation between variables, value distributions, and the number of missing variables were considered. We used data simulation techniques to establish a variety of different compound scenarios for missing dichotomous variables and conducted real-data validation on two real-world medical datasets. We comprehensively compared the performance of eight imputation methods (mode, logistic regression (LogReg), multiple imputation (MI), decision tree (DT), random forest (RF),k-nearest neighbor (KNN), support vector machine (SVM), and artificial neural network (ANN)) in each scenario. Accuracy and mean absolute error (MAE) were applied to evaluating their performance. The results showed that missing mechanisms, value distributions and the correlation between variables were the main factors affecting the performance of imputation methods. Machine learning-based methods, especially SVM, ANN, and DT, achieved relatively high accuracy with stable performance and were of potential applicability. Researchers should explore the correlation between variables and their distribution pattern in advance and prioritize machine learning-based methods for practical applications when encountering dichotomous missing data.