Study Objectives The objectives of this study were to evaluate the performance of renal function estimating equations compared to measured creatinine clearance (CrCl) during pregnancy and postpartum and to evaluate which body weight (pre‐pregnancy weight (PPW), actual body weight (ABW), and ideal body weight (IBW)) provides the best performance. Design A retrospective study. Setting Collections tookplace in the University of Washington clinical research unit. Patients Women (n = 166) who completed ≥1 pharmacokinetic (PK) study with a 6–24 h measured CrCl during pregnancy and/or ≥3 months postpartum were included. Intervention CrCl was estimated utilizing estimated glomerular filtration rate (eGFR) and CrCl equations with common weight descriptors. Analyses included Bland–Altman, relative accuracies within 10% and 25%, and root mean squared error (RMSE). Overall performance was determined by summation of rank for evaluation parameters. Measurements and Main Results During pregnancy, correlations between measured CrCl and estimated CrCl were between 0.5–0.8; equations with slopes closest to one were Modification of Diet in Renal Disease (MDRD2; PPW and ABW) and Cockcroft‐Gault (CG) (PPW); and y‐intercept closest to zero was Preeclampsia Glomerular Filtration Rate (PGFR). The lowest bias was seen with CG (ABW), and the highest accuracy within 25% was CG (ABW). CG (PPW) had the lowest RMSE. Postpartum, the best correlation was found with MDRD2 (PPW), Chronic Kidney Disease Epidemiology Collaboration (CKD–EPI (ABW)), and CKD–EPI 2021 (PPW). For slopes closest to one, MDRD2 (ABW) was best, whereas the equation with y‐intercept closest to zero was CKD–EPI (ABW). CG (PPW) had the highest accuracy within 25%, and 100/serum creatinine (SCr) had the lowest bias. Based on overall performance, CG (PPW) was the best followed by CG (ABW) and PGFR during pregnancy and 100/SCr followed by CG (PPW) and CG (ABW) postpartum. Conclusion The new CKD–EPI 2021 equation did not perform well during pregnancy. When 24‐h CrCls are not available during pregnancy, CG (PPW or ABW) performed the best overall, whereas at 3 months postpartum, 100/SCr performed the best overall.