PURPOSE: To compare prospectively the results of deep sclerectomy (DS) vs deep sclerectomy with collagen implant (DSCI). METHODS: Randomized prospective trial involving 26 eyes (13 patients) with medically uncontrolled primary and secondary open angle glaucoma. Collagen implant was randomly assigned to one eye of each patient. RESULTS: The mean follow-up period was 49.5 (SD 20) months for the DS-treated eyes, and 56.5 (SD 14) months for the DSCI-treated eyes (P=0.4). The mean preoperative intraocular pressure (IOP) was 24.1 (SD 7) mmHg for the DS-treated eyes, and 25.3 (SD 6) mmHg for the DSCI-treated eyes (P=0.5). The mean IOP at the first postoperative day was 6.4 (SD 3) mmHg for the DS-treated eyes, and 3.7 (SD 2) mmHg for the DSCI-treated eyes (P=0.05). The mean IOP at 12 months postoperative day was 15.4 (SD 3) mmHg for the DS group, and 10.4 (SD 4) mmHg for the DSCI-treated eyes (P=0.04), while at 48 months it was 16 (SD 3) mmHg for the DS group, and 10 (SD 4) mmHg for the DSCI-treated eyes (P=0.005). Complete success rate, defined as an IOP lower than 21 mmHg without medication, was 38% (5/13 patients) at 48 months for the DS-treated eyes, and 69% (9/13 patients) for the DSCI-treated eyes. Qualified success rate: patients who achieved IOP below 21 mmHg with or without medication, was 69% (9/13 patients) at 48 months and 100% (13/13 patients) for the DSCI group. The mean number of medications was reduced from 2.4 (SD 0.8) to 1.1 (SD 1) after DS, and was reduced from 2.2 (SD 0.7) to 0.4 (SD 0.6) in the DSCI group (P=0.001). For those eyes treated with DSCI, IOP was 3.21 mmHg lower than for those treated with DS (P<0.0001). CONCLUSION: The use of a collagen implant in DS seems to enhance the success rates, provides significantly lower IOP levels, and lowers the need for postoperative medications.