BACKGROUND: Laboratory monitoring for toxicity among patients receiving antiretroviral therapy (ART) in less-developed settings is technically challenging and consumes significant resources. METHODS: We conducted a cohort study of the 1800 adult patients who initiated ART at the Haitian Study Group for Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) in Haiti from 2003 to 2006, using baseline data to establish the prevalence and using follow-up data to establish the incidence of hepatitis, renal insufficiency, hyperglycemia, anemia, neutropenia, and thrombocytopenia. We determined how frequently routine (not symptom-driven) testing detected significant laboratory abnormalities and calculated the cost per disability-adjusted life year (DALY) averted by detection of these events in the asymptomatic stage, compared with a strategy of symptom-prompted testing only. RESULTS: Forty-eight patients (3.5%) had severe anemia at baseline testing and consequently did not receive zidovudine. Fifty-three patients receiving zidovudine therapy developed severe anemia during follow-up (incidence, 2.5 cases/100 person-years). Monitoring for asymptomatic anemia with hematocrit testing was cost-saving at baseline and had a cost-effectiveness ratio of US$317/DALY averted during follow-up; with a complete blood count, costs increased to US$1182 and $10,781/DALY averted, respectively. With glucose monitoring, 11 patients were diagnosed with new-onset hyperglycemia during follow-up (incidence, 0.7 cases/100 person-years), resulting in a cost-effectiveness ratio of US$9845 per DALY averted. Monitoring for asymptomatic hepatitis and renal insufficiency was expensive and rarely affected care. CONCLUSIONS: Resource-poor countries should select which laboratory tests to perform on the basis of the cost-effectiveness of each test. This will depend on the national ART drug regimen and the prevalence of other comorbidities. Routine monitoring with multitest hematological and chemistry panels is unlikely to be cost-effective.