Background: “Rules of thumb” for the replacement of electrolytes, including magnesium, in critical care settings are used, despite minimal empirical validation of their ability to achieve a target serum concentration. This study’s purpose was to evaluate the effectiveness and safety surrounding magnesium replacement in medically, critically ill patients with mild-to-moderate hypomagnesemia. Methods: This was a single-center, retrospective, observational evaluation of episodes of intravenous magnesium replacement ordered for patients with mild-to-moderate hypomagnesemia (1.0-1.9 mEq/L) admitted to a medical intensive care unit from May 2014 to April 2016. The primary effectiveness outcome, achievement of target serum magnesium concentration (≥2 mEq/L) compared to expected achievement using a “rule of thumb” estimation that 1 g intravenous magnesium sulfate raises the magnesium concentration 0.15 mEq/L, was tested using 1-sample z test. Logistic regression analysis was conducted to assess the effect of infusion rate on target achievement. Results: Of 152 days on which magnesium replacements were provided for 72 patients, a follow-up serum magnesium concentration was checked within 24 hours in 89 (58.6%) episodes. Of these 89 episodes, serum magnesium concentration reached target in only 49 (59.8%) episodes compared to an expected 89 (100%; P < .0001). There was no significant association between infusion rate and achievement of the target serum magnesium concentration (odds ratio: 0.962, 95% confidence interval: 0.411-2.256). Conclusions: Medically, critically ill patients who received nonprotocolized magnesium replacement achieved the target serum magnesium concentration less frequently than the “rule of thumb” estimation predicted.