The European Society of Reproduction emphasizes adequate management of anxiety for successful in-vitro fertilization (IVF). Although beta-blockers (BBs) have recently been approved and increasingly used for these symptoms, their potential to increase insulin resistance may adversely affect embryo implantation. Using a Korean healthcare database, we identified all women who underwent their first IVF cycle (2017–2023). Among these individuals, those with ≥1 prescription of beta-blockers within 84 days before an IVF cycle initiation were classified as users, while all others were classified as non-users (overall cohort). Then, we restricted the study cohort to women diagnosed with mental disorders to identify the potential effect of indications (restricted cohort). Clinical outcome was implantation success rate. Adjusted relative risks (aRRs) with 95% confidence intervals (CIs) were estimated by log-binomial regression after weighting. A total of 96,649 women were included, of whom 927 were prescribed BBs before their IVF cycle. In the overall cohort, users showed a significantly lower implantation success rate (aRR 0.87, 95% CI 0.77–0.99) compared with non-users. However, in the restricted cohort (users: n = 367; non-users: n = 2,102), no significant difference was observed (1.01, 0.80–1.27). Findings suggest no association between BB use and implantation failure. This evidence highlights the importance of mental health management for reaching pregnancy.