Aims and objectives To determine the medium-term effects of nurse case management on the dependence and satisfaction of patients with complex chronic disease and on caregiver burden. Background Caregiver exhaustion increases the readmission rate of highly dependent patients with complex chronic disease and their consumption of primary care resources. Design An observational and analytical cohort study was undertaken in multimorbid patients. Methods Data were gathered on Barthel Index and Caregiver Burden Index scores, primary care resource consumption, readmission and mortality rates, and patient satisfaction with care and care continuity. Results were compared between nurse case-managed (n = 62) and control (n = 193) multimorbid patients using univariate and bivariate analyses. Results The study included 255 patients with complex chronic disease (24·32% in management cohort vs. 75·68% in control cohort). The nurse case-managed group had significantly lower Barthel Index and higher Caregiver Burden Index scores and a significantly longer hospital stay. At 90 days postdischarge, no significant intergroup differences were observed in Barthel Index or Caregiver Burden Index scores, primary care resource consumption, readmission rate or mortality rate; the case-managed patients showed a significantly higher satisfaction level with their care and its continuity. Conclusions Nurse case management prevents a postdischarge increase in the dependence of multimorbid patients and the burden of their caregivers. Relevance to clinical practice Application of nurse case management can reduce the readmission rate and primary care consumption of patients with chronic complex disease after their hospital stay and prevent an exacerbation of caregiver exhaustion.