This systematic review aims to appraise available clinical evidence on the efficacy and safety of wound infiltration with adjuvants to local anesthetics (LAs) for pain control after lumbar spine surgery. A database search was conducted to identify randomized controlled trials (RCTs) pertinent to wound infiltration with analgesics or miscellaneous drugs adjunctive to LAs compared with sole LAs or placebo. The outcomes of interest were postoperative rescue analgesic consumption, pain intensity, time to first analgesic request, and the occurrence of adverse events. Twelve double-blind RCTs enrolling 925 patients were selected for qualitative analysis. Most studies were of moderate-to-good methodological quality. Dexmedetomidine reduced analgesic requirements and pain intensity within 24 h postoperatively, while prolonged pain relief was reported by one RCT involving adjunctive clonidine. Data on local magnesium seem promising yet difficult to interpret. No clear analgesic superiority could be attributed to steroids. Τramadol co-infiltration was equally effective as sole tramadol but superior to LAs. No serious adverse events were reported. Due to methodological inconsistencies and lack of robust data, no definite conclusions could be drawn on the analgesic effect of local infiltrates in patients undergoing lumbar surgery. The probable positive analgesic efficacy of adjunctive dexmedetomidine and magnesium needs further evaluation.