Background Most previous studies, conducted in non-Middle Eastern populations, have suggested that increase in the number of parity/live birth(s) leads to cardiovascular disease (CVD) development, although this issue is still controversial among both sexes. Biologic and socioeconomic pathways were suggested to explain this association. We studied this issue among urban Iranian men and women. Methods In this population-based cohort study, included 3929 women and 2571 men aged ≥ 30 years, Data for number of parity/live birth(s) were obtained by standard questionnaire. Participants were then annually followed for CVD events. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HRs), and 95% confidence intervals (CIs) for the number of parity/live birth(s) and other traditional CVD risk factors. Results During more than 15 years of follow-up, 456 and 524 CVD events have occurred among women and men, respectively. Among women, a J-shaped association was found between the number of live births and incident CVD with the lowest risk for women with 2 live births. Among women in multivariate analyses, each unit increase in parity had a HR of 1.05 (CI: 1.01–1.10) and having ≥ 4 parities was associated with a HR of 1.86 (0.97–3.56, p-value = 0.061). Among men, in comparison with participants who had 1 child, multivariate HRs of having 2, 3 and ≥ 4 children were 1.97 (1.24–3.12), 2.08 (1.31–3.31) and 2.08 (1.30–3.34), respectively. Conclusion To the best of our knowledge, the current study is the first report of this issue in the Middle East and North Africa region, a region with high burden of CVD. It can now be suggested that the number of parity/live birth(s) is linked to CVD among the Iranian population, with this issue being more prominent among men. Further research is needed to support our results and clarify the pathways between the number of parity/live birth(s) and CVD development among Iranian populations by considering potential factors, especially psycho-socio-economic factors.