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Unsafe abortion is a major public health issue in Nigeria, where high unmet need for contraception and restrictive abortion laws in the Northern and Southern parts of the country result in many abortions occurring outside the formal healthcare system and often under unsafe conditions. Given the high demand for abortion services and barriers to formal care in Nigeria, it is valuable to understand how and where women access medical abortion and if their clinical outcomes differ across these settings. This study aimed to determine whether important clinical outcomes differ among women who access misoprostol alone from a patent medicine vendor (PMV) when compared with those who access it from a clinic. We conducted a prospective, non-inferiority cohort study of women aged 15-49 accessing a misoprostol-alone regimen from clinics and PMVs in three states of Nigeria. The primary outcome of interest was additional treatment to complete the abortion within 30 days of using misoprostol. We computed crude and adjusted risk differences in outcomes by group (clinic versus PMV), and if the 95% confidence intervals on the crude and adjusted risk differences did not cross the non-inferiority limit of 4%, we considered PMVs non-inferior to clinics in terms of additional treatment to complete the abortion. Women were recruited at the point of accessing misoprostol at a clinic or PMV. Follow-up by telephone to confirm pill use and assess clinical outcomes was done at three to seven days, 10-29 days, and 30-45 days after taking misoprostol. Over 11 months, we enrolled 1835 women, and complete data were available from 1572 women (824 from clinics and 748 from PMVs). The rate of additional treatment to complete the abortion was non-inferior for the PMV group (3.6%) compared with the clinic cohort (9.5%), with an adjusted risk difference of -6.2% (95% CI-12.4%- 0.1%). Although a small proportion of women in each cohort (<8%) reported visiting a health care professional after taking misoprostol, no complications were reported. Most women felt prepared for what would happen after the misoprostol (92% of both cohorts) and would recommend medical abortion to a friend (89% of the clinic cohort and 90% of the PMV cohort). Self-managed abortion with misoprostol alone from PMVs was comparable in safety, effectiveness, and acceptability to clinic-based care, in line with global evidence supporting self-management of abortion care. Retrospectively registered at ClinicalTrials.gov ID NCT04242212. Unsafe abortion remains a major public health issue in Nigeria. Restrictive abortion laws and limited access to contraception mean that many abortions happen outside the formal healthcare system, often under unsafe conditions. This study examined whether women’s clinical outcomes differed when they obtained abortion pills from a clinic compared to a patent medicine vendor (PMV). PMVs are drug sellers who lack formal pharmaceutical training but are allowed to sell certain medicines. We followed 1,572 women across three states in Nigeria who received abortion pills from either a clinic or a PMV. We found that self-managed abortion with pills received from PMVs can be as safe, effective, and acceptable as clinic-based provision for pregnancies under nine weeks. No abortion-related complications were reported by the study participants. These findings support global evidence that medication abortion can be managed successfully outside of clinical settings, even in restrictive contexts like Nigeria, where abortion services and post-abortion care are limited. Many women rely on PMVs to access abortion medication, and this study highlights the role they can play in expanding access to safe abortion in Nigeria.