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Children with special risk medical conditions (SRMC) are over-represented in influenza hospitalizations. A systematic review was undertaken to determine whether children with SRMCs experience greater complications or severity following influenza infection.Bibliographies of pertinent articles were searched in MEDLINE and EMBASE (1990 to March 2018) and contact made with the investigators of unpublished studies containing relevant data. Studies of children (aged ≤18 years) with a SRMC hospitalized with influenza were included. Outcomes were pneumonia, intensive care unit (ICU) admission, mechanical ventilation, neurologic outcomes (seizures, encephalopathy), death and length of stay in hospital or ICU.Twenty-two studies met inclusion criteria. Compared with healthy peers, children with SRMC had higher odds of ICU admission [pooled odds ratio (OR) 1.66 (95% confidence interval (CI): 1.25–2.21)], for mechanical ventilation [pooled OR 1.53 (95% CI: 0.93–2.52)] and death [pooled OR 1.34 (95% CI: 0.74–2.41)]. Additionally, children with SRMC were more likely to develop bacterial pneumonia (crude OR 1.7; 95% CI: 1.1–2.6) or experience prolonged hospital length of stay [adjusted rate ratio 1.75 (95% CI: 1.44–2.11)]. The level of GRADE evidence was low for all outcomes considered in this review.While there was evidence that ICU management and bacterial pneumonia increases in children with SRMC, evidence showing an increase in the probability of death or need for mechanical ventilation was inconsistent. Further research using large datasets should evaluate the impact of complications and associated morbidity from influenza in SRMC children.