Analyzing massive VAERS reports without medical context may lead to incorrect conclusions about vaccine adverse events (VAE). Facilitating VAE detection promotes continual safety improvement for new vaccines. This study proposes a multi-label classification method with various term-and topic-based label selection strategies to improve the accuracy and efficiency of VAE detection. Topic modeling methods are first used to generate rule-based label dependencies from Medical Dictionary for Regulatory Activities terms in VAE reports with two hyper-parameters. Multiple label selection strategies, namely one-vs-rest (OvsR), problem transformation (PT), algorithm adaption (AA), and deep learning (DL) methods, are used in multi-label classification to examine the model performance, respectively. Experimental results indicated that the topic-based PT methods improve the accuracy by up to 33.69% using a COVID-19 VAE reporting data set, which improves the robustness and interpretability of our models. In addition, the topic-based OvsR methods achieve an optimal accuracy of up to 98.88%. The accuracy of the AA methods with topic-based labels increased by up to 87.36%. By contrast, the state-of-art LSTM- and BERT-based DL methods have relatively poor performance with accuracy rates of 71.89% and 64.63%, respectively. Our findings reveal that the proposed method effectively improves the model accuracy and strengthens VAE interpretability by using different label selection strategies and domain knowledge in multi-label classification for VAE detection.