Aim: The study aimed to detect and quantify bisphenol A (BPA) leaching in salivary samples of patients undergoing clear aligner therapy (CAT) using four different commercially available sheets. Materials and methodology: Four different commercially available clear aligners namely Monoflex®, Erkodur®, Leone®, and Duran® were delivered to 20 volunteers who were grouped into (n = 5) group A, group B, group C, and group D, respectively. Salivary samples were collected immediately before aligner insertion (day 0) and at day 1, day 5, and day 7 after aligner wear. Comparisons were made between baseline (day 0) BPA levels and subsequent time points to assess the leaching kinetics of BPA from the clear aligners by liquid chromatography/mass spectrometry. Results: The overall mean leaching of 0.74 ± 0.33 ppm at T1 (day 1) was observed among four groups of aligners, while no leaching was detected at T5 (day 5) and T7 (day 7). Among the four groups, the highest leaching of 1.24 ppm was detected from Duran at T1 followed by Monoflex (0.76 ppm), Erkodur (0.56 ppm), and Leone (0.43 ppm). Conclusion: It can be concluded that leaching only during the first 24 hours of aligner usage was dominant compared to other time intervals. Among the aligners considered, Duran was found to be the least safe followed by Monoflex, Erkodur, and Leone. Clinical significance: Since aligners are expanding in usage it is important to consider their biocompatibility. Even though the results indicate minimal leaching of BPA, it has a cumulative negative effect when patients undergo prolonged treatment with aligners.