Objective: While an echogenic intracardiac focus (EIF) is associated with an increased risk of trisomy 21 (T21), the magnitude of that risk remains controversial, particularly in the setting of a low-risk triple screen (TS). The objective of this study is to define the risk of T21 in patients with a low-risk TS and an isolated EIF. Study design: A retrospective analysis was performed on patients presenting prior to 22 6/7 weeks of gestation. Patients met criteria for inclusion if an EIF was noted, a TS had been drawn, the anatomic survey was complete and was determined to be normal, and karyotyping or delivery occurred at Bellevue Hospital. A high-risk TS was defined as a risk of < 1:500, assuming a 2-fold increased risk in the setting of an isolated EIF. A low-risk TS was defined as a risk of > 1:500. Statistical analysis was performed using chi-square, with p values of <0.05 considered significant. Results: 7,318 anatomic surveys were performed. An EIF was identified in 584 patients (7.98%), of which 391 met the criteria for inclusion. Of the 391, 51% were Asian and 38% were Hispanic; 348 had a low-risk TS and 43 had a high-risk TS. Patients with an EIF and a low-risk TS had a significantly lower risk of having a T21 pregnancy compared to those with a high-risk TS and an EIF (0 vs. 2.3%; p = 0.004). Conclusion: An isolated EIF with a low risk TS is not associated with an increased risk of T21.