Background: Anaphylaxis is the more severe form of immediate hypersensitivity. It can be life-threatening and therefore requires fast and appropriate medical management. After a first hypersensitivity phase, a recurrence of symptoms without an elicitor re-exposure may occur, called a biphasic reaction. The aim of this study was to identify biological and clinical predictors of biphasic reactions in patients with anaphylaxis. Methods: We retrospectively compared patients with monophasic anaphylaxis to those with biphasic anaphylaxis from an allergology day hospital in a French university hospital between January 2017 and May 2020. Results: Among the 237 patients, the rate of biphasic reactions was 5.5% (n = 13). The odds of a biphasic reaction was increased with asthma (p = 0.021; odds ratio = 4 [95% confidence interval 1.05-14.81]) and loss of consciousness during anaphylaxis (p = 0.008) as compared with monophasic anaphylaxis. Basal tryptase levels were significantly higher with biphasic than monophasic anaphylaxis (p = 0.009). Conclusions: Asthma and unconsciousness during the first phase of anaphylaxis could be associated with a biphasic reaction . Elevated basal tryptase was linked to biphasic reactions, which should be further explored.