Background. Calendar trends in virologic failure (VF) among human immunodeficiency virus (HIV)-infected patients can help to evaluate the performance of healthcare systems and the need for new antiretroviral therapy (ART). We examined the time trend in the rate of VF beyond 6 months of ART between 1997 and 2011 in France. Methods. We included patients from the French Hospital Database on HIV who received at least 6 months of ART. VF was defined as 2 consecutive plasma HIV-RNA values >500 copies/mL or as 1 value >500 copies/mL followed by a treatment switch. We adjusted for patients' characteristics by fitting a multivariable generalized estimating equation logistic regression model with an exchangeable covariance matrix. Results. A total of 81 738 patients were enrolled, and median follow-up was 112.4 months. Median CD4 count was 333 cells/μL, and 23% of patients had HIV infection classified as Centers for Disease Control and Prevention stage C. Overall, 29.3% of patients received single/dual-drug ART initially, and 45.4% of patients experienced at least 1 episode of VF during follow-up. The percentage of patients with VF fell from 61.5% in 1997–1998 to 9.7% in 2009–2011 (P < .0001). Factors associated with the lower frequency of VF were recent calendar period, a higher contemporary CD4 cell count, and first-line regimens based on nonnucleoside reverse transcriptase inhibitors or integrase inhibitors. Conclusions. The proportion of HIV-infected patients experiencing VF during routine care fell markedly between 1997 and 2009–2011, to only 9.7%. This was attributed to the advent of fully active and better-tolerated antiretroviral drugs, and to national guidelines recommending rapid management of VF after mid-2000.