Resistance to adamantanes for treating influenza A(H3N2) has increased dramatically, worldwide, over the past 5 years. A comprehensive 10-year data set on the rise of adamantane-resistance in Hong Kong is reported. Nucleotide sequences encoding the M2-ion channel of influenza A(H3N2) were obtained from 281 H3N2 isolates collected from adamantane-naive children admitted to a teaching hospital in Hong Kong, between 1997 and 2006. These sequences were screened for the presence of recognized adamantane resistance-associated amino acid mutations (L26F, V27A, A30T, S31N, G34E). The amantadane (rimantadine is not used in Hong Kong) usage for this hospital during this period was also collated. Fifty-eight isolates harbored at least one of these resistance signatures, the majority (57/58) being S31N, which increased rapidly over 2003-2005 from 20% to 83.3%. Other amino acid mutations, not previously associated with adamantane resistance, were also found. In particular, I51V was found to rise in frequency, along with S31N, though the significance of this mutation remains uncertain at present. A rise in amantadane usage occurred in Hong Kong between 2000 and 2002, which slightly preceded the subsequent rise in adamantane-resistant influenza A(H3N2) isolates. This study shows a temporal correlation between increases in amantadane prescriptions and the prevalence of adamantane-resistant influenza A(H3N2) viruses in Hong Kong. The underlying reasons for these findings are unclear and similar studies are required elsewhere to elucidate these and prevent this spread of drug-resistance happening again in future.