While obstetric anal sphincter injury (OASI) is less frequent in parous compared to nulliparous women, it remains a major concern affecting quality of life of women worldwide. The aim of this study was to evaluate the association between birthweight (BW) difference between deliveries and risk of OASI in parous women. We performed a retrospective case-control study including parous women with at least one previous vaginal delivery who were diagnosed with OASI. The control group consisted of parous women who did not have OASI during vaginal delivery. Controls were matched in a 1:2 ratio by year of birth, maternal age, and parity. Medical history, obstetric background, and current labor-related data were compared. Further univariate and multivariable analyses were performed, assessing for risk factors for OASI. One hundred eight parous women who had a diagnosis of OASI and a control group of 216 parturients who delivered without OASI were included in the final analysis. Differences between the current BW and the preceding and maximal previous BW were evaluated. There were significantly higher rates of women who had a larger neonate with > 500 g difference between the current and previous BW in the OASI group than in those with no OASI (28.7% vs. 12.30%, respectively; p < 0.001). Following a multivariable analysis for the dependent parameter of OASI, the following parameters were found to be independently associated with OASI outcome: previous operative vaginal delivery, BW ≥ 90th percentile, and current BW ≥ 500 g compared to previous maximal BW. In parous women, neonatal BW increase between deliveries of > 500 g is associated with OASI.