The aim of this study was to evaluate the effects of pegbovigrastim injection (Imrestor, Elanco Animal Health, Greenfield, IN) on production parameters and postpartum disease occurrence (retained placenta, metritis, and displaced abomasum, and clinical mastitis (CM)). The study was conducted on a commercial Mississippi dairy from August 21, 2017, to March 31, 2018. Study cows (n = 270) were blocked by parity group (multiparous or primiparous) and randomly assigned to control (CON, n = 144) or treatment (IMR, n = 126). Ten ± 2 d before expected calving and again at calving, treated cows received 2.7 mL of Imrestor and CON cows received 2.7 mL of 0.9% saline. Milk yield (MY), fat, protein, lactose, solids nonfat percent, SCC, and body condition, hygiene, and lameness were evaluated weekly. Animals were evaluated for metritis twice weekly through rectal temperature (RT), palpation, and uterine discharge evaluation until 30 DIM. Other postpartum diseases were recorded by farm personnel. Milk composition and MY were analyzed as repeated measures in time with block, treatment, calving month, and lactation week included in mixed models. The LOGISTIC procedure was used to evaluate disease occurrence. Variables entered a model if P ≤ 0.1 when screened individually. Variables with P ≤ 0.15 were kept in the final model. Milk yield, fat, protein, lactose, SNF, and log SCC were not significantly affected by treatment (P = 0.62, 0.57, 0.24, 0.47, 0.34, and 0.49, respectively). The CM occurrence did not differ between treatments (P = 0.54) but only 17 cases were detected. The metritis logistic model contained treatment, block, and RT. Every 1°C temperature increase was associated with 2.57 times greater odds of developing metritis. Treated cows were 2.45 times more likely to develop metritis compared with control cows (P < 0.01). Cows given pegbovigrastim injections had increased odds of developing metritis, but no negative effects on milk production and composition were observed.