Background: Acute exacerbation during pregnancy is the most important risk factor for an unfavorable outcome of pregnancy in women with asthma. Objective: We sought to identify pregnancy-related risk factors for acute exacerbations of asthma during pregnancy. Methods: Since 2007, all pregnant women referred to give birth at Hvidovre Hospital, Denmark, have been offered participation in the prospective Management of Asthma during Pregnancy (MAP) program. Women were included in the present analysis if they fulfilled the following criteria: (1) diagnosed with asthma, (2) prescribed at least rescue bronchodilator, and (3) had the first visit to the respiratory outpatient clinic within the first 18 weeks of pregnancy. Data were analyzed using multiple logistic regression models with backward stepwise elimination (Proc Logistic procedure in SAS). Results: Over an 8-year study period, a total of 1283 pregnancies in 1208 women fulfilled the criteria for inclusion in the MAP cohort. Women with asthma exacerbation(s) had larger gestational weight gain (GWG) in the first trimester of pregnancy (P <.001) and increased total GWG (P <.001) compared with women without exacerbation. More than 5 kg first-trimester weight gain was associated with an increased risk of asthma exacerbation (odds ratio, 9.35; 95% CI, 6.39-13.68; P <.001), and the risk increased in a dose-dependent manner with additional weight gain in excess of 5 kg. Conclusions: Excessive GWG in the first trimester is a risk factor for asthma exacerbation during pregnancy and the risk increases in a dose-dependent manner with increasing GWG.