The foam's structural longevity, linked to the effectiveness of sclerotherapy, depends on preparation conditions. The factors enhancing the treatment's effectiveness and efficacy are still under discussion. We conducted an invitro preclinical research, which included 144 independent trials. A total of 8 combinations involving 18 trials were designed according to settings of +4°C and room temperature (20-22°C), liquid-to-air ratios of 1/1 and 1/4, and polidocanol concentrations of 0.5% and 1% using the modified Tessari method. Our study aimed to examine the effect of air ratio, agent temperature, and polidocanol concentration on stability by assessing the foam half-time (FHT) and defining the optimal preparation conditions. The mean FHT was 117 ± 30.4 s. The longest FHT was in a 1:4 air-to-sclerosant ratio at +4°C, regardless of the sclerosant concentration (for %0.5 mean FHT: 146.2 ± 13.9 s, for % 1 mean FHT: 146.9 ± 18 s). There was a significant interaction among the three variables on FHT (p = 0.001). Temperature emerged as the primary factor (F(1, 136) = 124, p < 0.001, ηp2 = 0.477), with lower temperatures markedly enhancing the longevity (p < 0.001). Preparation at a temperature of 4°C resulted in an extended FHT of 32.5 s compared to 22°C (95% CI: 24.06-41.04 s). The temperature, agent concentration, and gas ratio significantly influence the stability of the physician-compounded foam. The low temperature at +4°C may offer better FHT for sclerotherapy.