Background: Most complex chronic total occlusions (CTOs) require the utilization of multiple recanalization strategies. However, data on wire manipulation time within CTO percutaneous coronary intervention (PCI) are limited. Objectives: We sought to investigate the impact of crossover time between crossing strategies on CTO PCI technical success. Methods: A total of 1026 patients admitted to our center between 2013 and 2019 for CTO PCI were assessed, of whom 143 were included for analysis. In these patients, the primary antegrade approach was changed to retrograde within one procedure. The crossover time between strategies remained at the operator's decision. Results: In most cases the target vessel was the right coronary artery (72%), followed by the left anterior descending (18.2%) and left circumflex (9.1%) arteries. The mean J-CTO score was 2.1 ± 1.1. Logistic regression analysis was used to estimate the odds of technical success associated with various crossover times. The results showed that 33 minutes was the threshold of the initial timing at which to review crossover of antegrade to retrograde recanalization of CTO. The odds of technical success with earlier crossover were 3.4 times higher 95% confidence interval (CI): 1.3 to 8.6. The chances of success reduced by 3% for every 1 minute longer than the threshold time (odds ratio: 0.97; 95% CI: 0.94 to 0.99, p = 0.05). Conclusions: Crossover to the retrograde approach should be considered no later than 33minutes after antegrade wire manipulation in order to maintain the maximum chances of final technical success.