We consider the problem of finding pairs of short patterns such that, in a given input sequence of length n, the distance between each pair’s patterns is at least α. The problem was introduced in [1] and is motivated by the optimization of multiplexed nested PCR. We study algorithms for the following two cases; the special case when the two patterns in the pair are required to have the same length, and the more general case when the patterns can have different lengths. For the first case we present an O(αn log log n) time and O(n) space algorithm, and for the general case we give an O(αn log n) time and O(n) space algorithm. The algorithms work for any alphabet size and use asymptotically less space than the algorithms presented in [1]. For alphabets of constant size we also give an O(n √ n log2 n) time algorithm for the general case. We demonstrate that the algorithms perform well in practice and present our findings for the human genome. In addition, we study an extended v...