The spread of drug-resistant HIV-1 might compromise the future success of current first-line regimens. To analyse the extent and impact of transmission of drug-resistant HIV-1 variants in Europe. The European prospective programme (SPREAD) collected demographic, clinical and virological data from 1245 HIV-1-infected individuals in 17 countries diagnosed in 2002-2003. The potential impact of transmitted drug resistance mutations (TDRMs) on therapy response was determined by using genotypic interpretation algorithms. The overall prevalence of viruses with drug-resistance mutations was 9.1% 96/1050; 95% confidence interval: 7.5-11.1. The majority (71%) harboured only a single amino acid substitution with limited effect on predicted drug susceptibility. Mutations associated with resistance to nucleoside reverse transcriptase inhibitors were observed most frequently 57/1050 (5.4%), followed by mutations related to protease inhibitors 32/1050 (3.0%) and mutations related to non-nucleoside reverse transcriptase inhibitors (NNRTIs) 27/1050 (2.6%). In some cases, however, resistance was quite extensive. Four individuals were infected with viruses with reduced susceptibility to all nucleoside reverse transcriptase inhibitors, 3 to all protease inhibitors and 20 to both NNRTIs. Remarkably, in one individual, the resistance pattern was so extensive that none of the available current antiretroviral drugs was predicted to be fully active. The prevalence of TDRM-HIV is quite prominent (9.1%) but did not increase in comparison with a large retrospective European study. Particularly the presence of single NNRTI mutations may impact the efficacy of the first-line regimens. Continuous prospective monitoring remains indicated to explore the patterns and factors contributing to the transmission of TDRMs as well as the potential clinical consequences.