Exposure to cold and hot temperatures is known to have negative impacts on human health. It is the aim of the present study to assess the health effects of cold and hot temperatures on the population living in the city of Isfahan. Daily data on average temperature and mortalities during the nine-year period 2008-2016 were obtained. Mortalities were stratified by causes (non-accidental, cardiovascular, respiratory, and stroke) and by age groups (0-14 years, 15-64 years, and ≥65 years). A standard time-series analysis was conducted using the Poisson model for cause-age-specific mortality effects of temperature, adjusted for seasonal and long-term trends as well as day of the week. Moreover, a distributed non-linear lag model (DNLM) with a 21-day lag time was used to determine the cumulative effects of cold and hot temperatures on mortality using the minimum mortality temperature (hereafter MMT) as the reference. A meta-analytical model was then used to pool the data thus obtained. Extreme temperatures were defied using cutoffs at 2.5th and 97.5th temperature percentiles and mortalities were reported as attributable to temperatures below and above MMT. A U-shaped curve was derived capturing the relationship between average temperature, on the one hand, and all the age and all the mortality cause groups, on the other. MMT was found to vary substantially for different age and cause groupings. Both cold and hot temperatures were found to increase the mortality risks, with a stronger effect of extreme temperatures. Cold temperature was responsible for a higher portion of the mortality than heat was. The cold effect on respiratory and stroke mortalities was higher than that on non-accidental and cardiovascular mortalities. Exposure to cold and hot temperatures increased relative risks of mortality in all age and cause groupings in Isfahan. Our findings can have important implications for mortality prevention in Isfahan.