AIMS: To determine the association between ambient temperature and severe hypoglycemia. METHODS: This was a prospective observational study performed in a prehospital setting. Data from the Emergency Medical Service in Hamburg (Germany) and data from the local weather station were evaluated over a 5-year period. Lowess-regression analysis was conducted to assess the relationship between ambient temperature and frequency of severe hypoglycemia. Additionally, three temperature-ranges were defined in order to compare them with each other with regard to frequency of severe hypoglycemia (<10 degrees C vs. 10-20 degrees C vs. >20 degrees C). RESULTS: In 2592 patients severe hypoglycemia was diagnosed and treated by emergency physicians (T1DM: n=829/32%; T2DM: n=1763/68%). The median age of patients was 64 (57-72 [20-85]) years. Compared to mild temperatures (10-20 degrees C) the frequency of severe hypoglycemia increased significantly at temperatures above 20 degrees C (+18% (95%-CI: [7%; 22%], p=0.007) and below 10 degrees C (+15% (95%-CI: [6%; 24%], p<0.001). CONCLUSIONS: The results suggest the existence of a "thermal comfort zone" covering a temperature range from 10 to 20 degrees C in which the frequency of severe hypoglycemia was significantly lower than below 10 degrees C and above 20 degrees C.