Abstract Background Fibrinogen reconstitution after therapeutic apheresis has been poorly studied. Apheresis modalities, for example, plasma exchange (PE), double‐filtration plasmapheresis (DFPP), or selective immunoadsorption (IA), may have different impacts. Methods We retrospectively investigated therapeutic apheresis sessions performed at our center across four modalities (PE, DFPP, and IA with or without plasma filtration). Fibrinogen levels were assessed at the beginning and end of each apheresis session, and immediately before the subsequent session. We adjusted measurements on hematocrit values to account for hemoconcentration. Results Between January 10, 2016 and March 2, 2020, we included 90 patients for a total of 754 apheresis sessions (PE: 35; DFPP: 351; IA only: 109; IA + plasma filtration: 259). Each patient received a median of five sessions (1Q 3; 3Q 9); median plasma volume treated was 5.5 L (1Q 4.3 L; 3Q 7.0 L). Within a session, DFPP and PE induced a significantly greater depletion of fibrinogen than both IA modalities, even after adjustment for the treated plasma volume. Median fibrinogen reconstitution was 0.8 (0.4‐1.2) g/L (median time between sessions: 38 hours). In multivariate analysis, fibrinogen reconstitution was significantly associated with intersession time (+0.66 g/L/log‐hour P < .001), apheresis modality (ANOVA; P < .001), initial fibrinogen concentration (+0.15 g/L per gram of fibrinogen; P < .001), and the last fibrinogen concentration from the previous apheresis session (−0.14 g/L per gram of fibrinogen; P < .001). In a model that considered hemoconcentration, the results were unchanged. Conclusions We demonstrate that fibrinogen reconstitution was highly variable between patients and apheresis sessions. Apheresis modalities had a significant impact on fibrinogen reconstitution, regardless of hemoconcentration.