OBJECTIVES: There is an urgent need to understand the costs associated with supporting, implementing, and maintaining the system redesign of small and medium sized safety-net clinics, which are serving 20 million patients in the United States. The study aimed to understand the characteristics of safety net primary care clinics that transformed into PCMHs, the trend of cost before and after PCMH transformation and the incremental cost for this transformation process in the Greater New Orleans. METHODS: The study sample was 110 primary care clinics, which received grant from the Primary Care Access and Stabilization Grant (PCASG) program (09/21/2007-09/20/2010) to support their PCMH transformation. The study period was divided into baseline (09/21/2007-03/21/2008), transformation (03/22/2008-03/21/2009) and maintenance (03/22/2009-09/20/2010) period and data were collected at six-month intervals. Baseline characteristics for the clinics later transformed into PCMHs were compared to those who did not. Trend analysis and econometric models (i.e., fixed-effect difference-in-difference models) were conducted for cost estimation, controlled for baseline differences by propensity score weights. RESULTS: Among the 110 clinics, 38% (41/110) achieved NCQA PCMH recognition by the end of the study period. The clinics which transformed into PCMHs had higher total cost, more clinic visits and a larger female patient proportion ($156,771 vs $47,823; 2,741 visits vs 785 visits, 59.71% vs 47.22%, all p<0.001) at baseline. The estimated incremental costs for clinics which underwent PCMH transformation was $37.61 per visit per six months, and it overall cost PCASG grant $24.86 per visit per six month to support a clinic’s transformation into PCMHs. CONCLUSIONS: Larger sized and higher female proportioned safety-net clinics likely transform into PCMHs. The PCASG program provided approximately $23.73 per visit over the three years. This estimated incremental cost could be used as a reference to guide future policy implementation for supporting primary care transformation in the United States.