Background We tested whether pre-HAART viraemia affects the achievement and maintenance of virological success in HIV-1-infected patients starting modern first-line therapies. Methods A total of 1,430 patients starting their first HAART (genotype-tailored) in 2008 (median; IQR: 2006–2009) were grouped according to levels of pre-HAART viraemia (≤30,000, 30,001–100,000, 100,001–300,000, 300,001–500,000 and >500,000 copies/ml). The impact of pre-therapy viraemia on the time to virological success (viraemia ≤50 copies/ml) and on the time to virological rebound (first of two consecutive viraemia values >50 copies/ml after virological success) were evaluated by Kaplan–Meier curves and Cox regression analyses. Results Median pre-HAART viraemia was 5.1 log₁₀ copies/ml (IQR 4.5–5.5), and 53% of patients had viraemia >100,000 copies/ml. By week 48, the prevalence of patients reaching virological success was >90% in all pre-HAART viraemia ranges, with the only exception of range >500,000 copies/ml (virological success =83%; P<0.001). Higher pre-HAART viraemia was tightly correlated with longer median time to achieve virological success. Cox multivariable estimates confirmed this result: patients with pre-HAART viraemia >500,000 copies/ml showed the lowest hazard of virological undetectability after adjusting for age, gender, pre-HAART CD4⁺ T-cell count, transmitted drug resistance, calendar year and third drug administered (adjusted hazard ratio [95% CI]: 0.27 [0.21, 0.35]; P<0.001). Pre-HAART viraemia >500,000 copies/ml was also associated with higher probability of virological rebound compared with patients belonging to lower viraemia strata at weeks 4, 12 and 24 ( P=0.050). Conclusions At the time of modern HAART, and even though an average >90% of virological success, high pre-HAART viraemia remains an independent factor associated with delayed and decreased virological success. Patients starting HAART with >500,000 copies/ml represent a significant population that may deserve special attention.