We examined the instability of organ donation decisions made by next-of-kin and factors that predict whether non-donors wish they had consented to donation. Next-of-kin of donor-eligible individuals from one organ procurement organization participated in a semi-structured telephone interview. Participants were asked if they would make the same decision if they had to make it again today. Of the 147 next-of-kin donors, 138 (94%) would make the same decision again; 6 (4%) would not consent to donation, and 3 (2%) were unsure. Of the 138 next-of-kin non-donors, 89 (64%) would make the same decision again, 37 (27%) would consent to donation, and 12 (9%) were unsure. Regret among non-donors was more likely when the next-of-kin had more favorable transplant attitudes (OR=1.76, CI=1.15, 2.69), had the first donation discussion with a non-OPO professional (OR=0.21, CI=0.13, 0.65), was not told their loved one was dead before this discussion (OR=0.23, CI=0.10, 0.50), did not feel they were given enough time to make the decision (OR=0.25, CI=0.11, 0.55), had not discussed donation with family members (OR=0.30, CI=0.13, 0.72), and had not heard a public serve announcement about organ donation (OR=0.29, CI=0.13, 0.67). OPOs should consider targeting these variables in educational campaigns and donation request approaches.