Nonsteroidal anti-inflammatory drugs are frequently avoided by some investigators in protocols for medical abortion because of a concern over potential inhibition of prostaglandin action on uterine contractions. To evaluate the effects of nonsteroidal anti-inflammatory drugs on uterine cramping and resultant pregnancy expulsion, analgesic use by 449 participants with gestational age of ≤56 days in three previously reported medical abortion trials involving methotrexate and misoprostol was reviewed. Subjects from each of the three trials were included in this analysis only if they received 50 mg/m 2 methotrexate intramuscularly followed 3 or 7 days later by 800 μg misoprostol vaginally. Misoprostol administration was repeated if the abortion did not occur after the first misoprostol dose. A total of 416 subjects met the study criteria. For the women who took a nonsteroidal anti-inflammatory drug after the first dose of misoprostol, 132246 (53.7%) aborted within 24 h. For those that did not take a nonsteroidal anti-inflammatory drug, 83170 (48.8%, p = 0.38) aborted within 24 h. Similarly, 2756 (48.2%) of the women who took a nonsteroidal anti-inflammatory drug aborted within 24 h of the second dose of misoprostol. However, only 32145 (22.1%, p = 0.002) of the women who did not take a nonsteroidal anti-inflammatory drug aborted. Use of a nonsteroidal anti-inflammatory drug does not interfere with the action of misoprostol to induce uterine contractions and pregnancy expulsion in women receiving methotrexate and misoprostol for early abortion.