This paper investigates the acetone variability in the upper troposphere (UT) as sampled during the CARIBIC airborne experiment and simulated by the LMDz- INCA global chemistry climate model. The aim is to (1) describe spatial distribution and temporal variability of acetone; (2) propose benchmarks deduced from the observed data set; and (3) investigate the representativeness of the observational data set. According to the model results, South Asia (including part of the Indian Ocean, all of India, China, and the Indochinese peninsula) and Europe (including Mediterranean Sea) are net source regions of acetone, where nearly 25% of North Hemispheric (NH) primary emissions and nearly 40% of the NH chemical production of acetone take place. The impact of these net source regions on continental upper tropospheric acetone is studied by analysing CARIBIC observations of 2006 and 2007 when most flight routes stretched between Frankfurt (Germany) and Manila (Philippines), and by focussing over 3 sub-regions where acetone variability is strong: Europe-Mediterranean, Central South China and South China Sea. Important spatial variability was observed over different scales: (1) east-west positive gradient of annually averaged acetone vmr in UT over the Eurasian continent, namely a factor two increase from east to west; (2) ocean/continent contrast with 50% enhancement over the continents; (3) the acetone volume mixing ration (vmr) may vary in summer by more than 1000 pptv within only 5 latitude-longitude degrees; (4) the standard deviation for measurements acquired during a short flight sequence over a sub-region may reach 40 %. ... mehrTemporal variability is also important: (1) the acetone volume mixing ratio (vmr) in the UT varies with the season, increasing from winter to summer by a factor 2 to 4; (2) a difference as large as 200 pptv may be observed between successive inbound and outbound flights over the same sub-region due to different flight specifications (trajectory in relation to the plume, time of day). A satisfactory agreement for the abundance of acetone is found between model results and observations, with e.g. only 30% overestimation of the annual average over Central-South China and the South China Sea (between 450 and 600 pptv), and an underestimation by less than 20% over Europe-Mediterranean (around 800 pptv). Consequently, annual budget terms could be computed with LMDz-INCA, yielding a global atmospheric burden of 7.2 Tg acetone, a 127 Tg yr−1 global source/sink strength, and a 21-day mean residence time. Moreover the study shows that LMDz-INCA can reproduce the impact of summer convection over China when boundary layer compounds are lifted to cruise altitude of 10– 11 km and higher. The consequent enhancement of acetone vmr during summer is reproduced by LMDz-INCA, to reach agreement on an observed maximum of 970±400 pptv (average during each flight sequence over the defined zone ± standard deviation). The summer enhancement of acetone is characterized by a high spatial and temporal heterogeneity, showing the necessity to increase the airborne measurement frequency over Central-South China and the South China Sea in August and September, when the annual maximum is expected (daily average model values reaching potentially 3000 pptv). In contrast, the annual cycle in the UT over Europe-Mediterranean is not reproduced by LMDz-INCA, in particular the observed summer enhancement of acetone to 1400±400 pptv after long-range transport of free tropospheric air masses over North Atlantic Ocean is not reproduced. In view of the agreement on the acetone annual cycle at surface level, this disagreement in UT over Europe indicates misrepresentation of simulated transport of primary acetone or biased spatial distribution of acetone chemical sinks and secondary sources. The sink and source budget in long-range transported free tropospheric air masses may be studied by analysing atmospheric chemical composition observed by CARIBIC in summer flights between North America and Europe.