BACKGROUND: South Asia is highly vulnerable to climate change and is projected to experience some of the highest increases in average annual temperatures throughout the century. Although the adverse impacts of ambient temperature on human health have been extensively documented in the literature, only a limited number of studies have focused on populations in this region. OBJECTIVES: Our aim was to systematically review the current state and quality of available evidence on the direct relationship between ambient temperature and heat waves and all-cause mortality in South Asia. METHODS: The databases Pubmed, Web of Science, Scopus and Embase were searched from 1990 to 2020 for relevant observational quantitative studies. We applied the Navigation Guide methodology to assess the strength of the evidence and performed a meta-analysis based on a novel approach that allows for combining nonlinear exposure-response associations without access to data from individual studies. RESULTS: From the 6,759 screened papers, 27 were included in the qualitative synthesis and five in a meta-analysis. Studies reported an association of all-cause mortality with heat wave episodes and both high and low daily temperatures. The meta-analysis showed a U-shaped pattern, with increasing mortality for both high and low temperatures, but a statistically significant association was found only at higher temperatures - above 31° C for lag 0-1 days and above 34° C for lag 0-13 days. Effects were found to vary with cause of death, age, sex, location (urban vs. rural), level of education and socio-economic status, but the profile of vulnerabilities was somewhat inconsistent and based on a limited number of studies. Overall, the strength of the evidence for ambient temperature as a risk factor for all-cause mortality was judged as limited and for heat wave episodes as inadequate. CONCLUSIONS: The evidence base on temperature impacts on mortality in South Asia is limited due to the small number of studies, their skewed geographical distribution and methodological weaknesses. Understanding the main determinants of the temperature-mortality association as well as how these may evolve in the future in a dynamic region such as South Asia will be an important area for future research. Studies on viable adaptation options to high temperatures for a region that is a hotspot for climate vulnerability, urbanisation and population growth are also needed.