The optimal resuscitative fluid remains controversial. To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; = 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; = 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; = 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; = 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; = 42%). Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.