It has been unexpectedly and surprisingly found that Helicase Dependent Amplification (HDA) primers having termini enriched for A or C at the 5′-ends, result in a much more efficient HDA reaction than those primers having G or T rich 5′-ends. Since A is a low melting base and C is a high-melting base, the melting characteristic of primer termini is not correlated with melting characteristics of amplicon termini. Optimized HDA primers, methods of making and using optimized primers, as well as methods of as well as kits for optimized HDA are disclosed.