Retail medicine clinics have become widely available. However, few studies have been published that compare retail clinic costs of care to standard medical visits for similar patients. The purpose of this study was to compare standard medical costs during a 6-month period after visiting a retail medical clinic to care received in a conventional medical office setting. Medical records of primary care patients (both adults and children) seen in a large group practice in Minnesota in 2008 were analyzed for this study. Two groups of patients were studied: those who used a retail walk-in clinic (N = 141) and a comparison group who used regular office care for same-day, acute visits (N = 137). Patients treated for 5 common conditions (pink eye, sore throat, viral illness, bronchitis, and cough) were selected. The dependent variables were standard costs using federal rates and the rank of standard costs. Multiple linear regression analysis was used to adjust for differences between groups. Median costs did not differ between sites ($126.30 for usual care and $88.10 for retail, P = 0.139); mean cost ranks were 132.5 for usual care and 115.6 for retail (P = 0.088). After adjusting for previous visit history, age, and sex, patients who received care in the retail setting had lower standard costs and lower cost rank than patients who received usual care (b = -52.9 [P = 0.006] and b = -24.5 [P = 0.021], respectively). After selection of cases with common conditions and adjustment for unequal variances, age, sex, and number of office visits in the previous 6 months, our retail clinic appeared to reduce medical costs for patients during the 6-month period after the index visit.