CONTEXT: The relative incidence of acute pancreatitis, ischemic cardiovascular disease and diabetes in hyperchylomicronemic patients exhibiting familial chylomicronemia syndrome (FCS), or multifactorial chylomicronemia syndrome (MCS), is unknown. OBJECTIVE: The objective was to study the occurrence of these events in FCS and MCS patients compared with the general population. METHODS: Twenty-nine FCS and 124 MCS patients, with genetic diagnosis, in four lipid clinics were matched with 413 controls. Individual hospital data linked to the national claims database were collected between 2006 and 2016. The occurrence of complications was retrospectively assessed before follow-up and during a median follow-up time of 9.8 years, for 1500 patient years of follow-up. RESULTS: FCS were younger than MCS (34.3 ± 13.6 vs 45.2 ± 12.6 years, p\textless0.01). During the study period, 58.6% of the FCS patients versus 19.4% of the MCS patients had at least one episode of acute hypertriglyceridemic pancreatitis (AHP) (HR=3.6; p\textless0.01). Conversely, the ischemic risk was lower in FCS than in MCS (HR=0,3; p=0.05). The risk of venous thrombosis was similar in both groups. The incidence of diabetes was high in both groups compared with matched controls (OR=22.8; p\textless0.01 in FCS and OR=30.3; p\textless0.01 in MCS). CONCLUSION: The incidence of AHP was much higher in FCS than in MCS patients, whereas the incidence of ischemic cardiovascular events was found increased in MCS both versus FCS and a representative matched control group. Differences in both triglycerides-rich lipoprotein metabolism and comorbidities in MCS vs FCS drive the occurrence of different patterns of complications.