Human parechoviruses (HPeVs) are frequent pathogens with a seroprevalence of over 90% in adults. Recent studies on these viruses have increased the number of HPeV types to eight. Here we analyse the complete genome of one clinical isolate, PicoBank/HPeV1/a, and VP1 and 3D protein sequences of PicoBank/HPeV6/a, isolated from the same individual 13 months later. PicoBank/HPeV1/a is closely related to other recent HPeV1 isolates but is distinct from the HPeV1 Harris prototype isolated 50 years ago. The availability of an increasing number of HPeV sequences has allowed a detailed analysis of these viruses. The results add weight to the observations that recombination plays a role in the generation of HPeV diversity. An important finding is the presence of unexpected conservation of codons utilized in part of the 3D-encoding region, some of which can be explained by the presence of a phylogenetically conserved predicted secondary structure domain. This suggests that in addition to the cis-acting replication element, RNA secondary structure domains in coding regions play a key role in picornavirus replication.