Prevalence of etravirine genotypic resistance was assessed among 92 HIV-1C-infected patients failing nevirapine and efavirenz-based regimens from a cohort of 552 Indian patients. Overall, prevalence of etravirine cross-resistance identified using the Tibotec Weighted Score was 41% (31.5% intermediately-resistant and 9.8% fully-resistant). The most frequently described nonnucleoside reverse transcriptase inhibitor-associated mutations included Y181 (35.9%), K101 (20.7%), G190 (17.4%), and V108 (15.2%). The resistant group demonstrated higher viral load (P = 0.01) and longer duration of antiretroviral treatment (P = 0.03) compared with the susceptible group.