Background: Patient activation is an important precursor not only for effective self-management of chronic comorbidity but also to empower patients in actively making decisions concerning their health. Studies report that increased activation in terms of high patient activation measure (PAM) scores are associated with increased patient engagement with the health care system, better compliance to treatment protocols, and improved health outcomes. This study aims to evaluate outcomes of Patient-Centred Medical Home model called ‘WellNet’ on activation levels of patients with multimorbidity in general practices across Sydney, Australia. Methods: A total of 636 patients consented to participate in the WellNet program delivered across six general practices in Northern Sydney, Australia. The WellNet treatment comprised of a team-based care with General Physicians collaborating with trained Chronic Disease Management care coordinators. After a comprehensive assessment, the care team designed patient-tailored care plan with self-management support and care navigation according to the level of risk and health care needs. Level of patient activation was measured using the validated PAM 13-item scale at baseline and follow-up. A case-series design was employed to determine significant differences between baseline and 12-months using General Linear Models. Multiple imputation was used to compute missing follow-up scores using Markov Chain Monte Carlo (MCMC) algorithm known as fully conditional specification (FCS). Multivariate regression models were employed to identify significant predictors of activation at follow-up. Results: Of the 626 patients, 420 reported their PAM levels at follow-up. The adjusted model showed significant mean difference in PAM scores of 6.5 (95%CI 5.0-8.1; p-value<0.001) after controlling for baseline covariates. Multivariate regression models determined that older age (OR = -0.14; 95% CI -0.28, -0.01), baseline activation score (OR = 0.48; 95% CI 0.37, 0.59), and private insurance (uninsured patients) (OR = -3.41; 95% CI -6.50, -0.32) were significant predictors of patient activation at follow-up. Conclusion: The WellNet study is the first of its kind in Australia to report on changes in the activation and self-management among patients with multimorbidity. PCMH has the potential to improve patient activation and engagement which can lead to long-term health benefits and sustained self-management behaviours.