Smooth muscle cell (SMC) proliferation is one of the major histopathological features in coronary restenosis lesions (REST). We hypothesized that SMC cultures derived from REST would proliferate at higher rate than those from de novo lesions; and that higher proliferative rates of SMC cultures may indicate patients at increased risk of post-procedural coronary restenosis. Methods: This study utilized atherectomy specimens obtained from 100 patients, 84 presented with de novo lesions, and 16 with REST. Primary cultures were successful in total of 29.0% expiants (25.0% and 50.0% respectively). Proliferation rates were determined by assessing the growth curves (between 4 and 6 passages) using a Coulter Counter. Results: SMC derived from de novo lesions expressed significantly lower proliferative rates than those derived from REST (p<0.05). In 43.8% of cultures derived from de novo lesions, growth was accelerated to a rate comparable with cells derived from REST. SMC derived cultures from 6.1% of de novo and 25% of REST remained viable with low proliferation rates. Conclusions: SMC cultures derived from restenotic human coronary lesions proliferated significantly faster than those derived from de novo lesions. Clinical correlation is required to determine whether faster proliferating SMC cultures from de novo or restenotic lesions would identify patients at higher risk of restenosis.