This study aimed to explore coping strategy profiles used by frontline medical workers and the psychological stress reactions associated with each category, in the COVID-19 pandemic context. Participants were 651 frontline medical workers recruited between February and March 2020. Psychological stress reactions (e.g., anxiety, depression) and coping strategies were assessed and analyzed using latent profile analysis and linear regression. Participants had three coping strategy profiles: coping inadequately (28.9%), coping appropriately (64.4%), and coping excessively (6.7%). Compared with coping appropriately, those who coped inadequately and excessively had higher psychological stress reactions levels. Levels of anxiety, depression, and posttraumatic stress disorder in excessive-coping individuals were higher than those who coped inadequately. Our findings elucidate the effectiveness of different coping strategy profiles and provide insights for developing targeted interventions to mitigate stress among medical workers. In light of these results, we recommend implementing stress management programs tailored to specific coping strategy profiles.