Objective: To compare the presentation, management, and outcomes of appendicitis in pregnant and non-pregnant females of childbearing age (18–45 years). Methods: This was a post-hoc analysis of a prospectively collected database (January 2017–June 2018) from 28 centers in America. We compared pregnant and non-pregnant females' demographics, clinical presentation, laboratory data, imaging findings, management, and clinical outcomes. Results: Of the 3,597 subjects, 1,010 (28%) were of childbearing age, and 41 were pregnant: The mean age of the pregnant subjects was 30 ± 8 years at a median gestational age of 15 (range 10–23) weeks. The two groups had similar demographics and clinical presentation, but there were differences in management and outcomes. For example, in pregnant subjects, abdominal ultrasound scans (US) plus magnetic resonance imaging (MRI) was the most frequently used imaging method (41%) followed by MRI alone (29%), US alone (22%), computed tomography (CT) (5%), and no imaging (2%). Despite similar American Association for the Surgery of Trauma Emergency General Surgery Clinical and Imaging Grade at presentation, pregnant subjects were more likely to be treated with antibiotics alone (15% versus 4%; p = 0.008). Pregnant subjects were less likely to have simple appendicitis and were more likely to have complicated (perforated or gangrenous) appendicitis or a normal appendix. With the exception of index hospital length of stay, there were no significant differences between the groups in clinical outcomes at index hospitalization or at 30 days. Conclusion: Almost 1 in 20 women of childbearing age presenting with appendicitis is pregnant. Appendicitis most commonly affects women in early to mid-pregnancy. Compared with non-pregnant women of childbearing age, pregnant women presenting with appendicitis undergo non-operative management more often and are less likely to have simple appendicitis. Compared with non-pregnant patients, they have similar clinical outcomes at both index hospitalization and 30 days after discharge.