Background: Obesity is a major contributor to medical comorbidity and places a large economic burden on health care. This study examined the effectiveness of primary care-integrated health coaching for weight loss in overweight/obese patients. Participants/Methods: This observational clinical study with a retrospective comparison analysis was performed at an urban academic primary care practice. A total of 271 individuals with a BMI >25 kg/m2 were recruited and followed for 2 years. A standardized health coaching intervention was used to promote weight loss. The main outcome measures were weight loss as a percentage of initial body weight and proportion of patients with weight loss ≥5% initial body weight, controlling for relevant covariates. An activity-based cost assessment of health coaching for weight loss was also performed. Results: Health coaching was associated with a mean loss of 7.24% initial weight after 12 months (95% CI = 8.68 to 5.90) and 6.77% after 24 months (95% CI = 8.78 to 4.76). Coached patients were more likely to achieve ≥5% of initial weight loss at both 12 and 24 months (P < .001). Health coaching costs were $288.54 per participant over 1 year. Conclusions: Primary care-integrated health coaching was associated with statistically significant weight loss in overweight and obese adults.