Abstract Purpose Home-LITE compared long-term treatment at home with tinzaparin or usual care in terms of efficacy, safety, patients' treatment satisfaction, incidence of post-thrombotic syndrome, and associated venous leg ulcers. Methods This multicenter, randomized, controlled trial enrolled 480 patients with documented, acute, proximal deep vein thrombosis. Patients received tinzaparin 175 IU/kg subcutaneously once daily for 12 weeks, or tinzaparin for ≥5 days plus oral warfarin, commenced on day 1, international normalized ratio-adjusted, and continued for ≥12 weeks (“usual care”). Patients received 1 in-clinic injection, then home treatment. Results The rate of recurrent venous thromboembolism at 12 weeks was 3.3% in both groups (absolute difference 0%; 95% confidence interval −3.2-3.2), and at 1 year was 10.4%/8.3% in the tinzaparin/usual-care groups, respectively (difference 2.1%; 95% confidence interval −3.1-7.3). There were no between-group differences in deaths at 12 weeks or 1 year, or bleeding at 12 weeks. Patients in the tinzaparin group expressed significantly greater treatment satisfaction ( P = .0024), particularly regarding freedom from the inconvenience of blood monitoring; were less likely to report signs/symptoms of post-thrombotic syndrome (individual odds ratios 0.66 to 0.91, overall odds ratio 0.77, P = .001); and reported fewer leg ulcers at 12 weeks: 1 (0.5%) versus 8 (4.1%) ( P = .02) with usual care. Conclusions Long-term home treatment with tinzaparin or usual care resulted in similar rates of recurrent venous thromboembolism, death, and bleeding. The significantly lower incidence of post-thrombotic syndrome and leg ulcers observed in the tinzaparin group is a potentially important benefit and deserves further study.