BACKGROUND: Antiretroviral (ART) scale-up in Malawi has been achieved on a large scale based mainly on clinical criteria. Simple markers of prognosis are useful, and we investigated the value of very early anthropometric changes in predicting mortality. PRINCIPAL FINDINGS: Adult patients who initiated ART in Karonga District, northern Malawi, between September 2005 and August 2006 were included in a prospective cohort study, and followed for up to one year. We used Cox regression to examine the association between anthropometric changes at 2 and 6 weeks and deaths within the first year. 573 patients were included, of whom 59% were women; the median age at initiation was 37 and 64% were in WHO stage 4. Both body mass index (BMI) and mid-upper arm circumference (MUAC) increased linearly with increased time on ART, and were closely correlated with each other. There were 118 deaths. After 2 weeks on ART, a BMI increase of <0.5 kg/m(2) (HR 2.47, 95%CI 1.24-4.94, p=0.005) or a MUAC increase of <0.5cm (HR 2.79, 95%CI 1.19-6.55, p=0.008) were strong predictors of death, and these associations were stronger after adjusting for baseline charactertistics. Similar results were found after 6 weeks on ART. CONCLUSIONS: Very early anthropometric changes, after 2 and 6 weeks on ART, are strong predictors of survival, independent of baseline characteristics. This should help identify patients requiring more detailed assessment where facilities are limited. MUAC is particularly valuable, requiring the simplest equipment and being appropriate for patients who have problems standing.