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PURPOSE To perform a mixed methods review to evaluate the effectiveness and implementation of models for integrating palliative care into ambulatory care for US adults with noncancer serious chronic illness. METHODS We searched 3 electronic databases from January 2000 to May 2020 and included qualitative, mixed methods studies and randomized and nonrandomized controlled trials. For each study, 2 reviewers abstracted data and independently assessed for quality. We conducted meta-analyses as appropriate and graded strength of evidence (SOE) for quantitative outcomes. RESULTS Quantitative analysis included 14 studies of 2,934 patients. Compared to usual care, models evaluated were not more effective for improving patient health-related quality of life (HRQOL) (standardized mean difference [SMD] of 4 of 8 studies, 0.19; 95% CI, -0.03 to 0.41) (SOE: moderate) or for patient depressive symptom scores (SMD of 3 of 9 studies, -0.09; 95% CI, -0.35 to 0.15) (SOE: moderate). Models might have little to no effect on patient satisfaction (SOE: low) but were more effective for increasing advance directive (AD) documentation (relative risk, 1.52; 95% CI, 1.35 to 1.94) (SOE: moderate). Qualitative analysis included 5 studies of 145 patients. Patient preferences for appropriate timing of palliative care varied; costs, additional visits, and travel were considered barriers to implementation. CONCLUSION Models might have little to no effect on decreasing overall symptom burden and were not more effective than usual care for improving HRQOL or depressive symptom scores but were more effective for increasing AD documentation. Additional research should focus on identifying and addressing characteristics and implementation factors critical to integrating models to improve ambulatory, patient-centered outcomes. Key words: palliative care; ambulatory care; mixed methods review; meta-analysis, INTRODUCTION In the United States, most care for adults with noncancer serious chronic illness occurs in ambulatory settings, particularly in clinicians' offices. Populations with serious chronic illness and conditions include, [...]