Disbudding is a common management procedure performed on dairy farms, and when done without pain mitigation is viewed as a key welfare issue. Although use of pain control is increasing, full adoption of anesthesia and analgesia has not been achieved. The objective of this systematic review was to examine the effects of pain control practices for cautery disbudding on outcomes associated with pain, specifically: plasma cortisol concentration, pressure sensitivity of the horn bud, and validated pain behaviors. Intervention studies describing cautery disbudding in calves 12 wk of age or less were eligible, provided they compared local anesthesia, non-steroidal anti-inflammatory drug (NSAID), or both, to one or more of local anesthesia, NSAID, or no pain control. Of the 4,394 records identified, 21 articles comprising 23 studies were eligible for qualitative synthesis. Meta-analysis was performed for all outcomes measured at similar time points with more than 2 comparator groups. Local anesthetic was associated with reduced plasma cortisol until 2 h post-disbudding (30 min, n = 7 studies; 1 h, n = 8; 2 h, n = 5); however, a rise in cortisol was observed in the meta-analysis of studies reporting at 4 h post-disbudding (n = 5). The addition of NSAID to local anesthetic showed reduction in plasma cortisol at 4 h (n = 6), and a reduction in pressure sensitivity and pain behaviors in some analyses between 3 and 6 h post-disbudding (n = 3 to 6). Heterogeneity was present in several meta-analyses, including many examining pain behavior. This may reflect variation in measurement periods, and/or differences among NSAID treatments. Overall, a protective effect of local anesthetic was seen for acute pain, and the delayed rise in cortisol was mitigated by use of an NSAID, which also reduced pressure sensitivity and pain behaviors. These findings support the use of local anesthetic and an NSAID, but the magnitude and duration of the effect of NSAID treatment was not possible to deduce from the literature due to the variation between studies. We recommend adherence to reporting guidelines and consideration of more standardized outcome measurements, particularly for pain behaviors.