Administration of intravenous ferric carboxymaltose (FCM) for iron-deficient patients suffering heart failure with reduced ejection fraction (HFrEF) has been associated with transient hypophosphatemia. We sought to investigate and model the effect of intravenous FCM on phosphate levels in iron-deficient patients with HFrEF. In this single-center retrospective study, serum phosphate levels, recorded for clinical reasons, were collected out to 60 days following intravenous FCM. Hypophosphatemia was defined as a nadir serum phosphate level <0.64 mmol/L. This was further categorized as severe (0.4 to <0.64 mmol/L) and extreme (<0.4 mmol/L). Factors associated with hypophosphatemia and change in serum phosphate over time were explored. Of 173 patients included, 47 (27%) experienced hypophosphatemia, 44 (25%) were classified as severe, and 3 (2%) extreme. Risk of hypophosphatemia was increased for patients with a creatinine clearance between 60 and <90 mL/min (odds ratio, 2.3; 95% confidence interval, 1.0-5.5), while <60 mL/min was protective. The median time to nadir in patients who experienced hypophosphatemia was 8 (interquartile range, 4-16) days, with a return to baseline levels at 6 weeks. Biochemically relevant hypophosphatemia is common following a single dose of intravenous FCM. The median time to nadir was 8 days, and creatinine clearance may influence phosphate levels following intravenous FCM. These observations support the need to increase awareness among clinicians administering intravenous FCM to iron-deficient patients with HFrEF.