The function of skeletal muscle is of interest to a broad audience including scientists and the lay public. We recently used frog gastrocnemius muscle to study the potential salutary effects of acetaminophen on threshold, tetanus, and fatigue. Leopard frogs (grass frogs, Rana pipens) were purchased from licensed vendors and housed in AAALAC-accredited animal facilities until they were used in the experimental laboratory. Experiments were previously reviewed and approved by the Rutgers University IACUC. After euthanasia both gastrocnemius muscles were removed and suspended in a muscle apparatus immersed in either vehicle (frog Ringers physiological salt solution) or 0.5 mM acetaminophen solution. Acetaminophen-treated muscles significantly outperformed vehicle-treated muscles during all experimental conditions. Specifically, the acetaminophen-treated muscles generated greater force under voltage-dependent twitch conditions and during tetany and fatigue. We conclude that acetaminophen produces previously-unknown, salutary physiological effects in amphibian striated skeletal muscle. We encourage others to confirm these results, investigate potential mechanisms, and extend this study to determine acetaminophen’s effects on mammalian skeletal muscle.