Purpose: To compare IOP behavior after deep sclerectomy (DS) and trabeculectomy with the Crozafon-De Laage Punch (TP), using low-dosage intraoperative mitomycin C (MMC) in both techniques. Methods: The study was a prospective randomized clinical trial. All patients met inclusion and exclusion criteria, and were scheduled for glaucoma surgery. Forty patients were randomized to undergo either a nonpenetrating DS with MMC (DSMMC) (19 eyes) or a TP with MMC (TPMMC) (21 eyes). Postoperative examinations were performed at the 1st day, the 1st, 2nd and 3rd weeks and the 1st, 3rd, 6th, 9th and 12th months. Postoperative complications, number of antiglaucoma medications and the IOP level were checked at each control. Complete success (without antiglaucoma medications) and qualified success (with or without medications) were assessed at two target IOP levels, namely ≤21 and ≤17 mm Hg in both groups. Moreover, the success rates at ≤21 mm Hg target IOP level were compared with those from previous series of patients who had undergone DS without MMC (historical control group). Results: Data from all eyes were available until the 12th month. The mean preoperative IOP ± SD was 29.6 ± 5.8 mm Hg in DSMMC eyes, 28.0 ± 6.0 in TPMMC eyes; the mean IOP at the 1st postoperative day was 12.5 ± 4.2 and 13.9 ± 6.5 mm Hg, while at the endpoint the mean IOP was 14.5 ± 4.0 and 16.1 ± 3.8, respectively, with significant reduction (p < 0.0005) of the preoperative IOP in both groups. Complete success (≤21 mm Hg target IOP) in 15 eyes (78.9%) of the DSMMC group and in 15 eyes (71.4%) of the TPMMC group was respectively found, while qualified success was achieved in all the eyes. When a ≤17 mm Hg target IOP was considered, complete success in 12 eyes (63.1%) and 13 eyes (61.9%), and qualified success in 13 eyes (68.4%) and 15 eyes (71.4%) were found in the DSMMC and TPMMC groups, respectively. No significant intergroup differences were found in terms of success rate. There is no statistical significance in the Kaplan-Meier cumulative survival curves as for complete and qualified success rate in both surgical groups for a ≤17 mm Hg target IOP (log rank, p = 0.918 and p = 0.429, respectively). As for the frequency of postoperative complications, hypotony and shallow anterior chamber were significantly more frequent in TPMMC when compared with the DSMMC group. The historical comparison between the DSMMC group and simple DS cases shows no significant difference between the groups, with a mild positive trend in DSMMC when compared with DS eyes. Conclusions: Both techniques, DSMMC and TPMMC, control IOP efficaciously at our endpoint. Our results indicate that low-dosage MMC can be considered a mild enhancement of DS IOP lowering effect without any negative effect on the well-known intra- and postoperative safety of the technique.