Objective Outside pregnancy, nitrofurantoin, ciprofloxacin and sulfamethoxazole-trimethoprim (SMZ-TMP) are first-line therapy (FLT) for lower urinary tract infections (LUTIs). Optimal antibiotics for LUTI have been extrapolated based on expert opinion. Progression to pyelonephritis and adverse obstetric outcomes were compared between women who received FLT and those given alternative antibiotics. Methods This study includes a retrospective cohort of women with LUTI, including asymptomatic bacteriuria and acute cystitis at single health care system from July 2013 to May 2019. Women receiving FLT, defined as nitrofurantoin or SMZ-TMP, were compared with those receiving nonfirst-line therapy (nFLT). Primary outcome was progression to pyelonephritis. Secondary outcomes included pyelonephritis-related anemia, sepsis, length of stay, preterm birth (PTB), and low birth weight (LBW). Logistic regression was used to calculate odds of outcomes. Results Of 476 women, 336 (70.6%) received FLT and 140 (29.4%) received nFLT. Women receiving FLT were more likely having BMI ≥ 40 ( p = 0.04). Progression to pyelonephritis did not differ (5.8 vs. 8.2%; p = 0.44), nor did other pyelonephritis-related outcomes. After controlling for confounders, no difference in odds of progression to pyelonephritis was seen (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 0.42, 2.49). FLT was not associated with PTB or LBW (aOR 0.60, 95% CI 0.29, 1.26) after controlling for confounders. Conclusion Receipt of antibiotics other than nitrofurantoin or SMZ-TMP for LUTI in pregnancy was not associated with increased risk of progression to pyelonephritis, PTB, or LBW.