Pegbovigrastim injection (IMR) represents a new approach in overcoming mastitis. The objective of this study was to evaluate production parameters, overall health, time to first detected heat, and behavior of cows treated with IMR or a saline control. 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). Milk yield, fat, protein, lactose, solids nonfat percent, somatic cell count, and body condition, hygiene, and lameness were evaluated weekly. Animals were evaluated for metritis twice weekly via evaluation of rectal temperature, per rectum palpation, and uterine discharge until 30 days in milk. Farm staff recorded occurrence of other diseases. Neck tag and a leg tag, each with activity monitoring sensors, measured behavior and time to first detected estrus. The occurrence of clinical mastitis did not differ between treatments. Treated cows were 2.46 times more likely to develop metritis compared to control cows. Cows given IMR had increased odds of developing metritis, without altering mastitis occurrence, production parameters, behavior, and time to first heat in lactating dairy cows.