Background: Infertility and miscarriage are common complications in women with PCOS, and may be linked with metabolic status and thyroid function. However, the role of ANGPTL6 in PCOS-related infertility and miscarriage remains underexplored. Study assessed serum ANGPTL6 levels in Iranian PCOS patients and its association with miscarriage, infertility, and thyroid dysfunction. Methods: This case-control study included 116 PCOS women (58 with infertility, 58 with a history of miscarriage) and 58 non-PCOS controls. The measurement of ANGPTL6, adiponectin, fasting insulin, and other hormonal parameters were measured using ELISA. Parametric data were analyzed with t-tests and ANOVA, and non-parametric data with Mann-Whitney and Kruskal-Wallis tests. Correlations were assessed using Pearson and Spearman tests. Logistic regression was used predicted PCOS risk. A p<0.05 was considered statistically significant. Results: ANGPTL6 levels were significantly higher in the PCOS group (48.72± 21.41 ng/ml) and the PCOS-miscarriage subgroup (50.16±19.57 ng/ml) compared to the non-PCOS group (41.56±14.74 ng/ml). T4 levels were significantly lower in the PCOS group (2.5±1.9 μg/dl) compared to controls (3.9±4.6 μg/dl, p<0.001). No significant correlation was found between ANGPTL6 and thyroid function tests. A positive correlation was observed between ANGPTL6 and adiponectin in the PCOS group (p<0.01). Logistic regression showed a significant association between ANGPTL6 and the risk of PCOS (OR: 1.02, 95%CI: 1.002-1.038), even after adjusting for age, body mass index (BMI), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Conclusion: Elevated ANGPTL6 levels were correlated with PCOS. Future research is needed to explore the molecular pathways linking ANGPTL6 to PCOS and its interaction with metabolic biomarkers.