Shoot tip necrosis is a common problem during in vitro culture of woody plants and was described in Pistacia vera right from the start of its culture. It is a complex problem whose cause could not be found yet, in spite of the numerous attempts already made, and limits to a great extent its tissue culture. In this work, pistachio shoot tip necrosis is studied in three different culture media, as well as the effect of different factors (Ca-gluconate, bottom cooling, shoot number or aeration) on shoot tip necrosis. DKW medium performed better than MS or WPM media, possibly due to its greater Ca concentration (up to 3 times more). This can be the cause of the lack of effect of Ca additions in the form of Ca-gluconate to DKW medium on shoot tip necrosis and on other parameters: shoot quality, multiplication rate or number of internodes. However, any of these factors: bottom cooling, shoot number per flask, or the use of vented jars with a bigger volume, had improved shoot tip necrosis impact and shoot quality in a significant way related to the control, although no significant differences among them were found. The results are discussed in terms of the beneficial effect on pistachio tissue culture of both higher quantities of medium per shoot and an increase of transpiration and nutrient transport through the shoot.