Despite the widespread adoption of hormonal synchronization protocols that allow for timed artificial insemination (AI), detection of estrus plays an important role in the reproductive management program on most dairies in the United States. Increased physical activity is a secondary sign of estrus in dairy cattle, and a new generation of electronic systems that continuously monitor physical activity to predict timing of AI have been developed and marketed to the dairy industry. A variety of management and physiologic challenges inhibit detection of behavioral estrus on farms, but the prevalence of anouvular cows near the end of the voluntary waiting period is particularly problematic. Only 70% of lactating Holstein cows were detected in estrus when using an activity monitoring system, with the remaining 20% of cows classified as anovular and 10% ovulating without showing signs of activity. Mean time of AI in relation to ovulation based on the activity monitoring system was acceptable for most of the cows with increased activity, however, variability in the duration of estrus and timing of AI in relation to ovulation could result in poor pregnancy outcomes in some cows. Use of a Presynch–Ovsynch protocol for submission of cows for first AI has been widely adopted by dairies in the United States, and a combined approach in which AI based on activity is followed by submission of cows not detected with activity to timed AI after synchronization of ovulation may be an effective strategy for submission of cows to first AI. Based on a field trial on a large commercial dairy in the United States, the activity monitoring system detected 70% of cows with increased activity after the second PGF2α injection of a Presynch–Ovsynch protocol, however, cows inseminated to increased activity had fewer pregnancies per AI (P/AI) compared with cows with increased activity after the second PGF2α injection that received timed AI after completing the Presynch–Ovsynch protocol. Based on an economic model comparing reproductive management programs with varying levels of AI to estrus v. timed AI, the rate of estrus detection and the P/AI to inseminations based on AI to detected estrus v. timed AI affected the decision to inseminate based on activity v. timed AI. In conclusion, an activity monitoring system detected increased activity in about 70% of lactating Holstein cows on a large commercial dairy in the United States, however, synchronization of ovulation and timed AI was beneficial to inseminate cows not detected with increased activity by the activity monitoring system.