Climate, glacier mass balance and runoff are investigated in the Low-Arctic Mittivakkat Glacier catchment on Ammassalik Island, Southeast Greenland. High-resolution meteorological data from the catchment covering 1993–2005 and standard synoptic meteorological data from the nearby town of Tasiilaq (Ammassalik) from 1898–2005 are used. Within the catchment, gradients and variations are observed in meteorological conditions between the coastal and the glacier areas. During the period 1993–2005 about 15% lower annual solar radiation was observed in the coastal area. Further, decreasing mean annual air temperatures (MAAT) occur in the coastal area, indicating an approximately 20-d shorter thawing period. The higher lying glacier area, in contrast, experiences an increasing MAAT, an approximately 40-d longer thawing period and a 60-d longer snow-free period. The Mittivakkat Glacier net mass balance has been almost continuously negative, corresponding to an average loss of glacier volume of 0.4% yr−1. The total catchment runoff is averaging 1973±281 mm w.eq. yr−1, and around 30% of the runoff is explained by glacier net loss. Over the 106 years (1898–2004) MAAT has, on average, increased significantly in the catchment by 1.3°C. However, time periods of considerable variability occur. All seasons show increasing air temperatures, with the highest increase during winter season. The period 1995–2004 was the warmest 10-yr period within the last 60 yr, and 1936–1946 the warmest within the last 106 years. The calculated glacier net mass balance indicates an average glacier loss of 550±530 mm w.eq. yr−1, and 89 out of 105 mass balance years show a negative net mass balance. For the 106-yr period average runoff was estimated to be 1957±254 mm w.eq. yr−1.