To determine modifiable risk factors and incidence of obstetric anal sphincter injury (OASIS) in primiparous women. We performed a population-based retrospective cohort study, using data from the Danish Medical Birth Registry. The population consisted of primiparous women with a vaginal delivery in the time period 2000-2010. Univariable and multivariable logistic regressions were used to determine risk factors of OASIS. Main outcome measures were incidence of OASIS in first vaginal delivery, odds ratios for possible risk factors: age, body mass index, birthweight, head circumference, gestational age, presentation, induction of labor, oxytocin augmentation, epidural, mediolateral episiotomy, vacuum extraction, forceps, shoulder dystocia, and year of delivery. Of 214,256 primiparous women with a vaginal delivery, 13,907 (6.5%; 95% confidence interval [CI] 6.4-6.6%) experienced an OASIS. The incidence of OASIS increased in the time period (adjusted odds ratio [aOR], 1.02; 95% CI, 1.02-1.03; P < .0001, per year). We found a protective effect of epidural analgesia (aOR, 0.84; 95% CI, 0.81-0.88; P = .0001). Vacuum extraction without episiotomy was a significant risk factor of OASIS (aOR, 2.99; 95% CI, 2.86-3.12; P < .0001), and episiotomy was protective in vacuum-assisted deliveries compared with vacuum-assisted deliveries without episiotomy (aOR, 0.60; 95% CI, 0.56-0.65; P < .0001). Birthweight was found to be an important nonmodifiable risk factor (aOR, 2.76; 95% CI, 2.62-2.90; P < .0001). Epidural analgesia in itself was protective against OASIS. Vacuum extraction increased the risk of OASIS, although mediolateral episiotomy was protective when applied in deliveries assisted by vacuum extraction. Copyright © 2014 Mosby, Inc. All rights reserved.