Numerous anecdotal accounts and qualitative research studies have reported on post-vaccination menstrual irregularities in women of reproductive age. However, none have quantified the impact. This is the first systematic review and meta-analysis to quantify and characterize the menstrual irregularities associated with vaccination for women of reproductive age. A search on July 20, 2022, retrieved articles published between December 1, 2019, and July 1, 2022, from MEDLINE, Embase, and Web of Science. The included articles were studies with full texts written in English that reported on menstrual irregularities for vaccinated vs. unvaccinated women of reproductive age. The quality of the studies was evaluated using the Study Quality Assessment Tool for Observation Cohort and Cross-Sectional Studies. Four observational studies were included. Review Manager was used to generating a forest plot with odds ratios (ORs) at the 95% confidence interval (CI), finding statistically significant associations between vaccination and menstrual irregularities for 25,054 women of reproductive age (OR = 1.91, CI: 1.76–2.07) with a significant overall effect of the mean (Z = 16.01, p < 0.0001). The studies were heterogeneous with significant dispersion of values (χ2 = 195.10 at df = 3, p < 0.00001, I2 = 98%). The findings of this systematic review and meta-analysis are limited by the availability of quantitative data. The results have implications for treating women of reproductive age with menstrual irregularities and informing them about the potential side effects of vaccinations.