Hypertriglyceridemia (HTG) is considered within the top 5 etiologies in acute pancreatitis (AP), but the association of serum triglyceride (TG) levels with the clinical course of AP remains controversial. This study aims to examine the effect of TG levels on severity of AP. Patients were enrolled prospectively through APPRENTICE. High TG levels were defined based on the Endocrine Society Clinical Practice Guidelines. HTG was categorized as mild (serum TG levels 150?199 mg/dL), moderate (200?999 mg/dL), severe (1,000?1,999 mg/dL), and very severe (?2,000 mg/dL). Severity of AP was based on the revised Atlanta classification criteria. Additionally, early TG levels were measured in 764 subjects and found elevated in 342 (120 with mild
176, moderate
and 46, severe/very severe HTG). Patients with increased TG levels were younger (age ?60, 16.7 vs. 30.3%), more likely to be male (66.1 vs. 51.2%), with more frequent alcohol use (62.8 vs. 50.7%), and diabetes mellitus (30.2 vs. 12.3%
all <
em>
p<
/em>
? 0.005). Severe AP (24.9 vs. 10.0%), ICU admission (32.5 vs. 19.7%), and mortality (5.3 vs. 1.7%
all <
em>
p<
/em>
? 0.005) were more frequently seen in patients with elevated TG levels. Based on multivariable analysis, elevated TG levels were independently associated with severe AP (<
em>
p<
/em>
<
0.05). This large multicenter study confirms that elevated TG levels are associated with severe disease regardless of AP etiology.