Objective: The primary objectives were to (1) identify risk factors for surgical evacuation following medical termination of second-trimester pregnancies in Denmark and (2) assesses if these risk factors were able to explain the a priori observed variation in risk of surgical evacuation among Danish hospitals and the a priori observed decline in risk throughout time. The secondary objective was to estimate the risk of major surgery following second-trimester medical abortion. Study design: We conducted a nationwide cohort study including all pregnancies terminated with mifepristone/misoprostol in second trimester in women aged 15–49 years through the period 2006–2017 in Denmark. All included pregnancies were followed for eight weeks from induction. Data were retrieved from national health registers. Multiple logistic regression provided adjusted odds ratios (ORs) of surgical evacuation with 95% confidence intervals (CI). Risk of major surgery was assessed and reported descriptively. Results: Of 5702 abortions, 2934 (52%) underwent surgical evacuation. The proportion of surgical evacuations decreased linearly from 72% in 13th gestational week to 17% in week 22 (p < 0.001). Compared to 25–29-year-olds, a reduced risk of surgical evacuation was observed in the youngest age group, 15–19 years (OR 0.77; 95% CI 0.61–0.99), while the risk among women aged 30–49 years did not differ significantly from the reference group. Compared to nulliparas, women with a history of only vaginal deliveries with spontaneous delivery of placenta had a decreased risk of surgical evacuation, OR 0.79 (95% CI 0.68–0.92). The OR of surgical evacuation varied from 0.05 (95% CI 0.02–0.15) to 2.38 (95% CI 1.71–3.31) among the hospitals (Copenhagen University Hospital as the reference) and declined significantly throughout the study period (OR for one-year increase in calendar time 0.82; 95% CI 0.81–0.84). Of the 5702 abortions, ten (0.2%) underwent major surgery following medical induction, including one laparoscopy, three hysterotomies, five laparotomies, and one hysterectomy. Conclusion: Risk of surgical evacuation of second-trimester medical abortions decreased with increasing gestational age and was reduced in women aged 15–19 years as well as in women with a history of only vaginal deliveries with spontaneous delivery of the placenta. However, these risk factors could not explain the significant variation in risk of surgical evacuation among hospitals and the decline in risk by time, suggestive of an unwarranted variation in risk of surgical evacuation following second-trimester medical termination of pregnancy in Denmark. Major surgery following medical induction was uncommon. Implication: Risk of surgical evacuation following medical termination of second-trimester pregnancy declined by calendar time and varied among Danish hospitals. Risk factors for surgical evacuation could not explain the difference by time and site of induction, suggestive of an unwarranted variation in the risk of surgical evacuation following second-trimester medical abortions in Denmark.