<h3>Objectives</h3> In 2021, new virtual clinics proliferated, offering remote-only telehealth abortion care with synchronous (phone or video) or asynchronous (messaging) communication and mailed pills. However, few large US studies have evaluated their safety and effectiveness. <h3>Methods</h3> We evaluated the safety and effectiveness of medication abortions provided by three virtual clinics operating in 21 states. We reviewed electronic health records for consecutive patients served between April 2021 and January 2022 and also invited the patients to participate in longitudinal surveys. We used multivariable mixed-effects models to estimate effectiveness and safety rates. <h3>Results</h3> Among the 6,134 included medication abortion patients, 73% received asynchronous services. Among the 5,036 (82%) abortion patients with follow-up data, 18 (0.44%, 95% CI: 0.36%-0.52%) had abortions that were followed by a serious adverse event. Abortion outcomes were confirmed for 4,106 (67%) cases, among whom 114 (2.8%, 95% CI: 2.3%-3.3%) required additional intervention to complete the abortion and 7 (0.21%, 95% CI: 0.06%-0.37%) were diagnosed with ectopic pregnancies. Rates of effectiveness (3.0% vs. 2.1%, p=0.187) and serious adverse events (0.44% vs. 0.44%, p=0.991) were similar between asynchronous and synchronous care. Among the 1,592 survey participants, 29 (2%) reported they would have had to continue the pregnancy had they not had access to telehealth abortion. Among survey participants, 47 received medications but did not take them, and among those, 36 still had the pills. <h3>Conclusions</h3> This real-world evidence shows that telehealth medication abortion care is safe and effective. Telehealth can increase access to this vital service while maintaining patient safety.