Purpose: There is substantial conjecture regarding the clinical significance of packed red blood cell (PRBC) changes that occur during in vitro storage. Here, we present a meta- and systematic analysis of adult studies published between 1994 and 2015 with the aim of updating existing quantitative reviews and providing a comprehensive cover of the six most commonly studied outcomes—mortality, infection, renal dysfunction, multiple organ dysfunction syndrome (MODS), thrombotic complications and prolonged hospital length of stay. Methods: Computerised searches of Pubmed and EMBASE identified publications that reported target outcomes and PRBC storage duration prior to transfusion. Bibliographies of relevant literature were manually searched to incorporate missed studies. Randomised controlled trial (RCT) data was meta-analysed using a random effects model with Cochrane Collaboration Review Manager (RevMan) version 5.1 software. Observational investigations were systematically reviewed. Results: Sixty-four papers were selected covering 462,581 patients with the majority of studies being observational in nature. Meta-analysis of eight RCTs demonstrated a trend towards decreased mortality with stored PRBC transfusion; albeit this effect was not statistically significant (OR 0.91, 95 % CI 0.78–1.05, p = 0.20). In a small subset of intensive care unit (ICU), cardiac surgery and trauma patients; observational studies suggested that prolonged storage may be correlated with increased mortality. Trauma and cardiac surgery patients appeared to be most susceptible to the potential infectious complications of stored PRBCs. Stored PRBCs were unlikely to affect thrombotic complications or hospital length of stay. There were inadequate data to determine whether stored PRBCs had clinically relevant effects on renal dysfunction and MODS. Conclusion: Although literature presents a concerning picture of potential storage complications, current findings are too inconsistent to drive changes in clinical practice. Results from current RCTs will likely play a role in PRBC age guidelines for cardiac surgery and ICU patients. However, these studies may be less efficacious at detecting small effects that are limited to specific subpopulations.