Objective: To compare between conservative management and appendectomy for acute appendicitis during pregnancy by trimester. Design: Retrospective cohort study. Setting: 632 acute-care hospitals in Japan. Population: Pregnant women diagnosed with acute appendicitis. Methods: We conducted a large nationwide study using a national inpatient database from July 2010 to March 2022. Comparisons were conducted using multivariable analysis with generalized estimating equations. Main Outcome Measures: Preterm labor, preterm delivery, or abortion, antepartum hemorrhage, duration of hospitalization, and duration of antibiotic use. Results: 3,158 individuals were eligible. Proportions of conservative management versus appendectomy by trimester were 507 (49.1%) vs. 525 (50.9%) in the first, 690 (44.6%) vs. 856 (55.4%) in the second, and 337 (58.1%) vs. 243 (41.9%) in the third. In the second trimester, appendectomy had a higher rate of preterm delivery, preterm labor, or abortion (OR 2.91; 95% CI 1.62–5.25). Antepartum hemorrhage occurred more frequently for appendectomy in the first (OR 2.12; 95% CI 1.31–3.43) and third (OR 2.43; 95% CI 1.79–3.31) trimesters. Appendectomy had longer duration of hospitalization in the second (2.15 days; 95% CI 1.14–3.17 days) and third (3.97 days; 95% CI 2.22–5.71 days) trimesters. Antibiotic use duration was shorter for appendectomy in the first (−1.20 days; 95% CI −1.51 to −0.90 days) and second (−0.61 days; 95% CI −0.90 to −0.32 days) trimesters. Conclusions: Clinical outcomes of acute appendicitis during pregnancy vary by trimester. Considering the appendectomy risks, conservative management may be viable depending on the clinical context and trimester.