To investigate the relationship between isoniazid resistance and HIV infection in patients with tuberculosis, we evaluated data in the Los Angeles County tuberculosis registry on 1,506 patients for whom drug susceptibility results were available. Among 235 HIV-infected patients, isoniazid resistance was less common than in 1,271 patients who were HIV-seronegative or who had not been tested for HIV, with an unadjusted odds ratio of 0.3. After adjustment for other factors that affect drug resistance (ethnicity, country of birth, prior diagnosis of tuberculosis, and cavitation), the frequency if isoniazid resistance remained lower than that in patients without HIV infection, with an odds ratio of 0.4 (95% confidence interval, 0.2 to 0.8; p = 0.02). We conclude that in Los Angeles, a setting where there is no ongoing outbreak of drug-resistant tuberculosis, isoniazid-resistant tuberculosis is not more common in HIV-infected patients.