Three studies involving 352 grower pigs were conducted to determine the effects of dietary supplementation with multistrain spp. direct-fed microbial (DFM) and protease, alone or in combination, on growth performance, nutrient digestibility, blood characteristics, fecal microbiota, and noxious gas emissions, and to use a meta-analysis to increase the reliability of the findings. Treatments ( = 4) were set up as a 2 × 2 factorial design with 2 levels of protease (0 and 5.000/6.000 units/kilogram of feed [U/KG]) and 2 levels of DFM (0 and 1.5 × 10 colony forming units/gram of feed [CFU/G]), plus a protease + DFM combination. Pigs were housed in groups of 3 or 4/pen with 8 replicate pens/treatment. Experimental diets were fed for 42 d and feed intake and BW were measured weekly. Fecal samples were collected at d 42 and analyzed to determine apparent total tract digestibility (ATTD). Fecal counts of and coliforms, and noxious gas emissions were measured. Blood samples were taken by anterior vena cava puncture to measure blood urea nitrogen (BUN) and creatinine. Data from the 3 studies were pooled and analyzed as a 2 × 2 factorial using the Fit Model platform of JMP 11 (SAS Inst. Inc., Cary, NC). Means separation was determined using Tukey's honest significant difference test. The main effect of protease and DFM increased: BW at 42 d, overall ADG, and overall G:F compared to the control ( < 0.04). There were no interactions between protease and DFM ( > 0.05); however, the protease + DFM combination was the only treatment to improve ADG and G:F in all phases compared to the control. The main effect of protease increased ATTD of DM, nitrogen (N), and ADF ( < 0.04). The main effect of DFM increased ATTD of DM, N, GE, DE, ADF, and fat ( < 0.02). There was a trend for an interaction between protease and DFM for ATTD of GE and DE ( < 0.08) because the protease + DFM combination increased energy digestibility more than the additive effects of the protease and DFM alone. The main effects of protease and DFM decreased fecal ammonia emissions ( < 0.01), but the protease + DFM combination was the only treatment to decrease ammonia emissions compared to the control. In conclusion, the main effects of protease and DFM improved growth performance and nutrient digestibility compared to the control, but there was a greater additive effect of the protease + DFM combination on energy and N digestibility.