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Context: Thromboembolism in children with acute lymphoblastic leukemia (ALL) is most commonly reported after the initiation of antileukemic therapy, indicating a possible interaction of disease and therapy. Aims: To study the effect of induction chemotherapy on coagulation parameters in pediatric ALL patients. Settings and Design: Thirty-seven newly diagnosed patients of ALL up to 18 years of age were evaluated along with 30 age- and sex-matched controls. Subjects and Methods: At the time of diagnosis (day 0), various coagulation parameters were tested. These were sequentially analyzed on day 14 (after the completion of L-asparaginase doses) and on day 28 of therapy (after the completion of induction). Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C (PC) activity, and protein S (PS) activity were done by a clot-based method. Antithrombin (AT) assay was performed by chromogenic method. D-dimer (D-DI), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) levels were assayed by ELISA method. Statistical Analysis Used: The statistical analysis was done using Statistical Package for Social Sciences version 17.0. Results: No major change in PT and APTT was observed during chemotherapy; however, fibrinogen levels declined significantly (P = 0.04), following L-asparaginase treatment. D-DI levels were significantly raised at diagnosis (P < 0.001) and throughout induction therapy (P < 0.001). PC, PS, and AT were reduced in the initial part of induction, followed by a rise in the second half of therapy, reaching their respective baseline levels (P < 0.05). The tPA levels were significantly reduced in the patients at diagnosis and throughout therapy (P < 0.001). PAI-1 levels were comparable to controls at presentation and showed a rising trend during therapy. Conclusions: The results of this study indicated that both the malignant process and the drugs used in combined chemotherapy cause thrombin activation, decrease in natural inhibitors, and hypofibrinolysis, resulting in hypercoagulability. Thus, ALL per se is a hypercoagulable state and the prothrombotic condition at the time of diagnosis gets enhanced during induction chemotherapy.