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.