Buffering local anesthetics with epinephrine (Epi) offers clinicians options not often considered. This study assessed outcomes for pulpal anesthesia, pain on injection, and time to midface numbness for buffered 1% lidocaine with 1:100,000 Epi versus nonbuffered 2% lidocaine with 1:100,000 Epi. Materials and Methods: In this trial with a randomized, crossover design, buffered 1% lidocaine was compared with nonbuffered 2% lidocaine. Subjects were adult volunteers who served as their own controls. The predictor variables were alternate drug formulations. The outcome variables were subjects' responses to cold and electric pulp testing (EPT) stimulation of the maxillary first molar and canine, pain levels during the injection, and time to midface numbness. After maxillary field blocks with 40 mg of buffered lidocaine or 80 mg of nonbuffered lidocaine, subjects reported pain on injection and responses of the maxillary first molar and canine after cold and EPT stimulation. Teeth were tested before field block and at 30-minute intervals until a positive response was detected. Two weeks later, subjects were tested with the alternate drug combinations. For all outcome variables, assessment of treatment difference, calculated as 1% buffered minus 2% nonbuffered, was performed with the Wilcoxon rank sum test with significance at P < .05. Results: More of the 24 subjects were women and Caucasian. The median age was 23.5 years (interquartile range, 21, 25 years), and the median body weight was 155 lb (interquartile range, 128.5, 176.5 lb). Pain levels during the injection were significantly lower for 1% buffered lidocaine, with P = .04. Times to response after injection were not significantly different between the 2 drug formulations for the cold test on a molar, with P = .08, or the cold test on a canine, with P = .22. However, times to response were significantly longer for nonbuffered drugs for EPT on the molar and canine, both with P = .01. Conclusions: Buffering 1% lidocaine with 1:100,000 Epi reduces the pain on injection with a maxillary field block and results in similar lengths of pulpal anesthesia tested with a cold stimulus as compared with nonbuffered 2% lidocaine with 1:100,000 Epi.