Background and Objective The use of fibrinogen concentrate to treat or prevent major bleeding with regard to potential adverse reactions has not been free of controversy. Our objective was to perform a post-authorization safety study to describe the use of Clottafact ® (LFB Biomedicaments) fibrinogen concentrate in real-life medical practice in Mexico. Methods This was a prospective, observational study that collected and evaluated information between January 2017 and June 2019 related to suspected serious adverse reactions (SUSARs) during and after Clottafact ® infusion. Results Information from 40 subjects was analyzed; 43% were women (n = 17), mean age was 39.05 ± 26.8 years (range 0-91 years). The medical specialties included in this analysis were cardiac surgery − 52.5% of the cases, gynecology/obstetrics − 17.5%, general surgery and orthopedics − 12.5% each, and hematology and neurosurgery − 2.5%, respectively. Mean plasma fibrinogen levels before and after Clottafact ® infusion were 2.58 g/L and 4.02 g/L; p = 0.001, respectively. The mean Clottafact ® dose was 2.20 ± 0.77 g. One patient presented SUSARs (dry mouth and dysgeusia) with drug administration, which ceased after treatment discontinuation. Conclusions In this real-life post-marketing study, the safety profile of Clottafact ® was very similar to previous reports. Thus, Clottafact ® shows a favorable safety profile in clinical practice. Key Points Clottafact ® showed a favorable safety profile in clinical practice in Mexico. Clottafact® human fibrinogen concentrate usage profile is considered safe in real-world conditions for the treatment of acquired or congenital fibrinogen deficiency.