Negation and speculation unrelated to abnormal findings can lead to false-positive alarms for automatic radiology report highlighting or flagging by laboratory information systems. This internal validation study evaluated the performance of natural language processing methods (NegEx, NegBio, NegBERT, and transformers). We annotated all negative and speculative statements unrelated to abnormal findings in reports. In experiment 1, we fine-tuned several transformer models (ALBERT [A Lite Bidirectional Encoder Representations from Transformers], BERT [Bidirectional Encoder Representations from Transformers], DeBERTa [Decoding-Enhanced BERT With Disentangled Attention], DistilBERT [Distilled version of BERT], ELECTRA [Efficiently Learning an Encoder That Classifies Token Replacements Accurately], ERNIE [Enhanced Representation through Knowledge Integration], RoBERTa [Robustly Optimized BERT Pretraining Approach], SpanBERT, and XLNet) and compared their performance using precision, recall, accuracy, and F1-scores. In experiment 2, we compared the best model from experiment 1 with 3 established negation and speculation-detection algorithms (NegEx, NegBio, and NegBERT). Our study collected 6000 radiology reports from 3 branches of the Chi Mei Hospital, covering multiple imaging modalities and body parts. A total of 15.01% (105,755/704,512) of words and 39.45% (4529/11,480) of important diagnostic keywords occurred in negative or speculative statements unrelated to abnormal findings. In experiment 1, all models achieved an accuracy of >0.98 and F1-score of >0.90 on the test data set. ALBERT exhibited the best performance (accuracy=0.991; F1-score=0.958). In experiment 2, ALBERT outperformed the optimized NegEx, NegBio, and NegBERT methods in terms of overall performance (accuracy=0.996; F1-score=0.991), in the prediction of whether diagnostic keywords occur in speculative statements unrelated to abnormal findings, and in the improvement of the performance of keyword extraction (accuracy=0.996; F1-score=0.997). The ALBERT deep learning method showed the best performance. Our results represent a significant advancement in the clinical applications of computer-aided notification systems.