Medical diseases and depression frequently co-occur, but it remains uncertain whether specific medical diseases or the disease load, affect the clinical course of depression. We identified all adults (≥18 years) at their first hospital-based diagnosis of unipolar depression in Denmark between 1996 and 2015. All medical hospital contacts since 1977 and all drug prescriptions during the previous year were identified. We followed patients for up to five years regarding hospital admissions with depression and performed adjusted Cox regression analyses calculating hazard rate ratios (HRR) including 95%-confidence intervals (CI) to test the association between medical diseases and depression admission following the index depressive episode. Among 117,585 patients with depression (444,696 person-years follow-up), any prior medical hospital contact (N = 114,206; 97.1%) was associated with increased risks of admission for depression among individuals aged 18-30 (HRR=1.50; 95%CI=1.15-1.95), 31-65 (HRR=1.69; 95%CI=1.28-2.21), and >65 years (HRR=1.38; 95%CI=1.10-1.75), fitting a dose-response relationship (p<0.005) with increasing number of prior medical diseases among those aged <65. All specific medical diseases were associated with increased risks of admission for depression, particularly among individuals aged<65 (HRR ranging from 1.57 to 2.38). Drug prescriptions and medical hospital contacts in the year before the depression diagnosis were associated with reduced risks of admission. The medical load seems to be associated with an increased risk for depression admission, particularly among individuals aged <65. The lower risk for people in medical care during the previous year may indicate better compliance and care/treatment. Copyright © 2020. Published by Elsevier B.V.