AbstractObjective:Native Hawaiians and other Pacific Islanders (NHs/PIs) have a high obesity prevalence compared to other ethnic groups. We examined socio‐demographic, behavioral, and biological factors related to ≥3% weight loss in 100 overweight/obese NHs/PIs who completed a lifestyle intervention.Design and Methods:Data were from 56 Native Hawaiians, 22 Chuukese, and 22 Other Pacific Islanders who participated in a randomized controlled trial of the Partnership for Improving Lifestyle Intervention (PILI) 'Ohana Project. All completed a 3‐month weight loss program (WLP) to initiate weight loss and were then randomized into either a 6‐month family/community focused WLP called the PILI Lifestyle Program (PLP; n = 49) or a standard behavior WLP (SBP; n = 51). We collected baseline, 3‐ and 9‐month follow‐up data on socio‐demographics, weight (kg), a 6‐min. walk test, dietary fat, exercise frequency, and blood pressure.Results and Conclusion:Based on ANCOVA or logistic fit, ethnicity, sex, initial weight loss, fat in diet at baseline, change in systolic blood pressure, and intervention type were significantly associated (P ≤ .05) with ≥3% weight loss at 9‐month follow‐up. A logistic regression model indicated that Chuukese (OR = 6.04; CI = 1.14–32.17) and participants who had more weight loss in the first 3‐months (OR = 1.47; CI = 1.22–1.86) and who were in the PLP (OR = 4.50; CI = 1.50–15.14) were more likely to achieve ≥3% weight loss [model; χ2 (7, N = 100) = 45.50, P < .0001]. The same lifestyle intervention does not benefit all NHs/PIs equally, possibly due to differences in acculturation status and social support. The findings also point to the importance of initial weight loss to sustain motivation toward long‐term weight loss maintenance.